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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 5/4/2026 has been entered.
Applicant's arguments, filed 5/4/2026, have been fully considered. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Applicants have amended their claims, filed 5/4/2026, and therefore rejections newly made in the instant office action have been necessitated by amendment.
Claims 1-20 are the currently pending claims hereby under examination. Claims 1, 19, and 20 have been amended.
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.
Claims 1-5 and 13-17 are rejected under 35 U.S.C. 103 as being unpatentable over Elbadry et al. (US 2019/0358387 A1), hereinafter Elbadry, and further in view of Barat et al. ("Simultaneous high speed optical and impedance analysis of single particles with a microfluidic cytometer," Lab on a Chip 12 (2012): 118-126), hereinafter Barat, and further in view of Pal et al. ("Void fraction measurement using concave capacitor based sensor: Analytical and experimental evaluation," Measurement 124 (2018): 81-90), hereinafter Pal.
Regarding claim 1, Elbadry teaches a system for characterizing an effluent sample from a patient undergoing peritoneal dialysis (PD) (Elbadry, ¶[0008]: for peritoneal dialysis patients having a patient monitoring device connected to the dialysis catheter, a combination of sensors including optical scatter or absorption and conductivity sensors is used to monitor drainage dialysate and detect infection; ¶[0009]: a multitude of sensors is used to remotely monitor dialysis-related complications).
Elbadry further teaches a container for enclosing the effluent sample, wherein the container is configured such that all effluent from the patient flows through the container (Elbadry, ¶[0115]: the patient monitoring device may be coupled in-line with a drainage line to receive dialysate from the patient and pass it to a drainage vessel; Fig. 13; ¶[0121]: "the waste dialysate and fresh dialysate both flow through the same set of sensors"; ¶[0123]: in a drain-only variation, a set of sensors is connected only to the waste dialysate solution port and the patient monitoring device monitors only the drainage dialysate solution). The fluid conduit in this in-line drainage configuration encloses the drainage dialysate as the effluent passes from the patient through the monitoring device and onward along the drainage path.
Elbadry further teaches an optical system comprising a light source and a photodetector, the light source configured to emit a beam of radiation that passes through the container and irradiates the effluent sample, and the photodetector configured to detect the radiation after it irradiates the effluent sample to generate an optical signal (Elbadry, ¶[0022]: an optical sensor includes at least one emitter configured to transmit light through patient fluid flowing through a fluid conduit and at least one detector configured to receive the transmitted light and generate signal data; ¶[0023]: "the fluid conduit comprises at least one transparent portion"; ¶[0027]: an optical sensor may engage a conduit portion transparent to ultraviolet, visible, or infrared radiation; ¶[0124]: a glass tube segment may integrate with an optical scatter or absorption sensor). Elbadry therefore teaches transmission optical interrogation of the effluent flowing through the same fluid conduit serving as the claimed container.
Also, regarding claim 1, Elbadry does not fully teach an electrical system comprising a first pair of electrodes and a second pair of electrodes, wherein the first pair of electrodes and second pair of electrodes are attached to the container. Rather, Elbadry expressly teaches electrical sensing associated with the fluid conduit, including a conduit that integrates electrical sensors such as impedance and conductivity sensors (Elbadry, ¶[0124]). However, Elbadry does not expressly teach the claimed first and second electrode-pair arrangement attached to opposing portions of the fluid-containing structure.
Barat teaches a fluid sensing region having four electrically active electrodes integrated with opposing channel-forming surfaces. Barat teaches that "[t]wo pairs of electrodes are fabricated on the top and bottom of the channel, forming a differential measurement system" (Barat, p. 119, "Measurement principle"). Barat further teaches that the upper portion of the channel is connected to the electrical source and identifies the lower electrodes as "the measurement electrodes" (Barat, p. 122, discussion of Fig. 3; see also Fig. 1(c)). Accordingly, for purposes of the claimed arrangement, the two electrodes associated with the upper channel surface constitute the first pair of electrodes and the two electrodes associated with the opposing lower channel surface constitute the second pair of electrodes.
Barat additionally teaches that "[a] sinusoidal voltage of 1 Vpp at 1 MHz was applied to both pairs of electrodes and the current measured using custom built electronics and a lock-in amplifier" (Barat, p. 121, "Impedance system"). Barat uses "pair" in that statement according to its own designation of the opposed upper-and-lower electrode measurement locations. Consistent with that terminology, Fig. 1(c) shows electrical excitation delivered through the two upper electrodes and the resulting electrical response received through the two lower measurement electrodes. Thus, all four electrodes are electrically active components of Barat's measurement circuit even though the same four electrodes are grouped by channel surface for purposes of the presently claimed first and second pairs.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Elbadry in view of Barat to implement Elbadry's expressly contemplated conduit-integrated electrical sensing using Barat's four-electrode arrangement, with two electrodes forming a first pair attached to one portion of Elbadry's fluid conduit and two electrodes forming a second pair attached to an opposing portion of the conduit. Elbadry already calls for electrical sensing associated with the conduit carrying the patient fluid, while Barat teaches a known arrangement in which electrodes disposed on opposing channel surfaces cooperate to electrically interrogate fluid occupying the intervening sensing region. Barat further teaches simultaneous optical and electrical interrogation in the same sensing region. A person of ordinary skill would therefore have been motivated to use Barat's four-electrode arrangement as a known structural implementation of the electrical sensing already contemplated by Elbadry while retaining Elbadry's existing optical interrogation of the conduit.
The modification applies Barat's opposed electrode topology to Elbadry's existing fluid conduit and does not substitute Barat's microfluidic cytometer for Elbadry's drainage conduit or require adoption of Barat's channel dimensions, hydrodynamic focusing, or particle-position discrimination. Those features of Barat concern handling and discrimination of individual particles and are not the structural electrode teaching being applied. Elbadry continues to supply the in-line PD drainage conduit and flow path, while Barat supplies the arrangement of electrically active electrodes associated with opposing portions of the fluid-containing structure. Elbadry teaches glass or polymer conduit structures, and Barat forms its electrodes on glass channel structures, providing compatible fluid-containing wall materials for the proposed implementation.
Also, regarding claim 1, the modified Elbadry does not fully teach that the first pair of electrodes and second pair of electrodes are configured to measure a capacitance of the effluent sample to generate a capacitance signal. Rather, as modified in view of Barat, the modified Elbadry includes a first pair comprising two source-side electrodes attached to one portion of the conduit and a second pair comprising two measurement-side electrodes attached to an opposing portion of the conduit, with the first and second pairs cooperating to electrically interrogate the material between them. Barat operates this four-electrode arrangement to determine impedance and does not expressly configure the first and second pairs to determine capacitance of the effluent as the measured electrical quantity and generate a capacitance signal.
Elbadry itself, however, expressly teaches that capacitance sensing is useful for obtaining information concerning dialysis fluid. Elbadry teaches a creatinine sensor comprising interdigitated screen-printed carbon electrodes coated with an enzyme-responsive polymer and teaches that application of creatinine-containing samples produces changes in capacitance of the polymer-coated electrodes that are "analyte-concentration dependent," thereby providing a creatinine sensor (Elbadry, ¶[0298]). Elbadry further teaches that the same sensing system may be used for urea or other serum detection and that the measurement surface of the creatinine sensor is fluidically connected to the infusing dialysate solution and drainage dialysate solution (Elbadry, ¶[0298]). Thus, Elbadry expressly recognizes capacitance-responsive electrical sensing as useful for characterizing dialysis fluid, although Elbadry does not teach obtaining the claimed capacitance measurement using the Barat-derived first and second electrode pairs attached to opposing portions of the fluid conduit.
Pal teaches capacitance measurement of material within a nonmetallic fluid conduit using four electrodes associated with the conduit. Pal teaches that "[f]our concave electrodes (A, B, C, and D) are placed on the opposite sides of the pipe such that they will form two parallel plate capacitors" C_AC and C_BD (Pal, p. 82, §2.1). Pal further teaches that "two electrodes A and B acts as exciter electrodes and other two electrodes C and D act as measuring electrodes" (Pal, p. 82, §2.2). Accordingly, one capacitance measurement is obtained between exciter electrode A and measuring electrode C and another capacitance measurement is obtained between exciter electrode B and measuring electrode D. Each capacitance measurement therefore results from cooperation between an electrode of the exciter group and a corresponding electrode of the measurement group.
Pal further teaches that the resulting capacitances C_AC and C_BD vary according to the material occupying the pipe. Pal separately calculates capacitance paths C_NET AC and C_NET BD and experimentally measures corresponding capacitance values over the tested range (Pal, pp. 84-88, §§2.3-3.2, Tables 2-3). Pal explains that the measured capacitance depends upon the relative permittivities of the materials occupying the pipe and evaluates materials including water having a relative permittivity of approximately 80 (Pal, pp. 85-86, §2.5, Figs. 9(a)-9(b)). Thus, Pal teaches determining capacitance responsive to the dielectric properties of material contained within the pipe.
Pal further teaches that the disclosed capacitance-measurement technique can be used with “a variety of liquids (conductive or non-conductive),” that the electrode design can be modified according to the flow pattern within the pipe, and that capacitance-based sensors are practical in most types of fluids because of their simple design and accurate measurement (Pal, p. 82). Pal experimentally implements the four-electrode capacitance sensor with an acrylic pipe having a 94 mm internal diameter and a 100 mm outer diameter, thereby demonstrating capacitance measurement of material occupying a macroscale fluid conduit (Pal, p. 87, §3.1).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the modified Elbadry in view of Pal to configure the Barat-derived first and second electrode pairs to perform Pal's capacitance measurement, with the two electrodes of the first pair serving as respective excitation electrodes and the two electrodes of the second pair serving as respective measurement electrodes, thereby establishing a first capacitance-measurement path between a first excitation electrode and a corresponding first measurement electrode and a second capacitance-measurement path between a second excitation electrode and a corresponding second measurement electrode. Elbadry itself establishes that capacitance-responsive sensing is useful for obtaining information concerning dialysis fluid, Barat provides the four-electrode structure and the functional division between source-side and measurement-side electrodes, and Pal teaches that two exciter electrodes and two measuring electrodes may be operated in corresponding excitation-and-measurement paths to determine capacitance of material occupying a fluid-containing pipe. A person of ordinary skill would therefore have been motivated to apply Pal's conduit-compatible capacitance-measurement technique to the Barat-derived electrode arrangement as a known structural implementation of a capacitance-sensing modality already contemplated by Elbadry for analysis of dialysis fluid.
Both the first pair and second pair would thereby be configured as operative components of the capacitance measurement. Barat teaches that its four electrodes cooperate as a common electrical measurement system, with the first pair providing electrical excitation required for the measurement and the second pair receiving the corresponding electrical response. Pal likewise obtains each capacitance value through cooperation of one exciter electrode and one measuring electrode, such that capacitance paths C_AC and C_BD each extend between the exciter group and the measuring group. Neither group performs the respective capacitance measurement alone. Accordingly, the two groups cooperate to measure capacitance of the effluent sample and generate the resulting capacitance signal.
Although Pal applies its capacitance sensor to industrial fluid-flow measurement rather than dialysis effluent, Pal addresses the technical problem of configuring electrodes associated with a fluid-containing structure to obtain capacitance information responsive to material contained within the structure. Pal expressly teaches use with conductive and non-conductive liquids, adaptation of electrode geometry according to flow conditions, and a simple and accurate capacitance measurement technique (Pal, p. 82). A person of ordinary skill seeking to configure the electrodes associated with Elbadry's fluid-containing sensing region to obtain capacitance information concerning the monitored fluid therefore would reasonably have looked to Pal notwithstanding the different end use.
A person of ordinary skill would also have had a reasonable expectation of success because Pal demonstrates the capacitance technique on a 94 mm internal-diameter acrylic pipe, expressly teaches use with conductive and non-conductive liquids, and demonstrates dielectric-dependent capacitance measurements involving materials spanning a wide range of relative permittivities, including water (Pal, pp. 82, 85-88). Thus, the capacitance measurement does not depend upon Barat's micrometer-scale channel dimensions, hydrodynamic focusing, or particle-position discrimination. The modification retains Elbadry's existing in-line drainage conduit and optical sensing operation while using the Barat-derived electrode topology to perform Pal's independently demonstrated capacitance measurement.
Also, regarding claim 1, the modified Elbadry does not expressly teach a processor operating an algorithm configured to collectively process the optical signal and the capacitance signal to characterize the effluent sample. Rather, Elbadry teaches that "a combination of different signals and/or signals over time are generated from the sensor array and reported or analyzed to determine patient status" (Elbadry, ¶[0004]); expressly teaches using combinations including optical scatter or absorption and electrical conductivity measurements to monitor PD drainage dialysate and detect infection (Elbadry, ¶¶[0008]-[0009]); and teaches a microcontroller that receives and may analyze sensor outputs and a server processor that may analyze transmitted patient-monitoring data (Elbadry, ¶¶[0116]-[0117]). Elbadry additionally teaches capacitance-responsive sensing of dialysis fluid, including analyte-concentration-dependent changes in capacitance used for creatinine sensing (Elbadry, ¶[0298]). However, Elbadry does not expressly teach collectively processing an optical signal with the particular capacitance signal generated by the Barat-derived first and second electrode pairs operated according to Pal.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the modified Elbadry by including the capacitance signal generated by the Pal-derived electrical sensing arrangement among the different sensor signals collectively processed by Elbadry's existing processor. Elbadry expressly teaches analyzing combinations of sensor outputs to determine patient status, specifically teaches using optical and electrical measurements together when monitoring PD drainage dialysate, and independently recognizes capacitance-responsive sensing as providing analytically useful information concerning dialysis fluid. Once the Barat-derived electrode arrangement is configured according to Pal to generate a capacitance signal from the drainage dialysate, a person of ordinary skill would therefore have been motivated to include that electrical sensor output together with Elbadry's optical signal in the multisensor analysis that Elbadry already employs for characterization of the drainage dialysate.
Barat further supports the predictable use of those optical and electrical signals together because Barat teaches simultaneous acquisition and analysis of optical and electrical measurements from a common fluid sensing region. Thus, the proposed collective processing does not originate solely from the claimed invention. Elbadry already teaches collective multisensor processing, expressly combines optical and electrical measurements in its PD monitoring system, and independently recognizes capacitance as analytically useful electrical information, while Barat demonstrates simultaneous optical and electrical characterization of material in a common sensing region. The modification therefore applies those established multisensor teachings to the capacitance output produced by the Pal implementation of the Barat-derived electrode arrangement without changing the operation of Elbadry's drainage-monitoring system.
Regarding claim 2, as set forth above regarding claim 1, the modified Elbadry further teaches the container is a sample cell comprising at least two surfaces. Elbadry's fluid conduit includes a sensing region through which the drainage dialysate flows and in which the optical and electrical measurements are obtained. Barat teaches a fluid-containing sensing region bounded by opposing channel-forming surfaces, including an upper channel surface and an opposing lower channel surface on which its electrical electrodes are disposed (Barat, p. 119, "Measurement principle"; Fig. 1(c)). In implementing Barat's opposed-surface electrode topology in Elbadry's fluid-containing sensing region as set forth regarding claim 1, the resulting sensing region constitutes a sample cell containing the effluent sample and comprises at least the opposed first and second wall surfaces corresponding to Barat's upper and lower channel-forming surfaces. The same modification already made regarding claim 1 therefore provides the at least two opposed surfaces recited in claim 2 without requiring adoption of Barat's microscale channel dimensions.
Regarding claim 3, Elbadry further teaches each surface of the sample cell comprises an optically transparent material. Elbadry teaches optical sensing through a conduit portion transparent to ultraviolet, visible, or infrared radiation (Elbadry, ¶[0027]) and expressly teaches a glass tube segment integrated with an optical scatter or absorption sensor (Elbadry, ¶[0124]). In the glass sensing-segment implementation of Elbadry's fluid-containing sample cell established regarding claim 2, the opposed wall surfaces through which the transmission optical interrogation is performed are glass and therefore comprise optically transparent material.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have implemented the sensing portion of Elbadry's conduit using Elbadry's expressly contemplated glass tube segment. Elbadry identifies the glass segment specifically for integration with an optical scatter or absorption sensor, and therefore provides a known transparent wall material for the fluid-containing sensing region already modified to include Barat's opposed electrode surfaces. The modification would retain the same in-line drainage flow path while providing optical transmission through the sample-cell walls.
Regarding claim 4, Elbadry further teaches the optically transparent material is selected from a group consisting of glass, plastic, ceramic, diamond-based material, or derivatives thereof. In particular, Elbadry expressly teaches a glass tube segment integrated with an optical scatter or absorption sensor (Elbadry, ¶[0124]). Glass is expressly one of the materials recited in claim 4.
Regarding claim 5, the modified Elbadry does not expressly teach the first pair of electrodes and the second pair of electrodes are a thin film deposited on at least one of the two surfaces.
Barat teaches that "[t]wo pairs of electrodes are fabricated on the top and bottom of the channel, forming a differential measurement system" (Barat, p. 119, "Measurement principle"). Barat further teaches that "[m]etal electrodes consisting of 200 nm thick platinum with a 20 nm Ti seed layer were fabricated on 100 mm diameter glass wafers by photolithography" (Barat, p. 119, "System overview"). Barat therefore teaches forming the first and second electrode pairs as thin-film metal layers on the glass surfaces forming the fluid-containing sensing region.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the modified Elbadry in view of Barat to form the first and second electrode pairs as thin films on the surfaces of the sample cell. As set forth above regarding claim 1, Barat's opposed four-electrode arrangement is applied to implement the electrical sensing contemplated by Elbadry. Barat further teaches forming that same electrode arrangement as 200 nm platinum layers with 20 nm titanium seed layers on glass wafers. A person of ordinary skill would therefore have been motivated to use Barat's disclosed thin-film fabrication when implementing Barat's electrode arrangement in Elbadry because it provides a known manner of forming the selected electrode architecture directly on glass surfaces of a fluid-containing sensing region. Barat demonstrates successful fabrication of those thin-film electrodes on glass substrates, and Elbadry expressly contemplates a glass tube segment for its sensing region, providing compatible substrate materials for the proposed implementation. The modification would retain the electrode arrangement and sensing functions established regarding claim 1 while providing the thin-film construction recited in claim 5.
Regarding claim 13, Elbadry teaches the optical system is further configured to measure an optical absorption of the effluent sample. Elbadry expressly teaches optical absorption sensing for monitoring PD drainage dialysate (Elbadry, ¶[0008]); a glass tube segment integrated with an optical scatter or absorption sensor (Elbadry, ¶[0124]); and that fluid characteristics including optical absorption may be measured in a non-fluid-contact manner (Elbadry, ¶[0127]). Elbadry further identifies Fig. 35 as an exemplary absorption spectrum of components of effluent (Elbadry, ¶[0063]).
Regarding claim 14, Elbadry does not fully teach the processor is configured to analyze the radiation after it irradiates the effluent sample and determine the amount of radiation absorbed by the effluent sample. Rather, Elbadry teaches the light source is configured to emit the beam of radiation that passes into the effluent sample, and the photodetector is configured to receive the radiation after it irradiates the effluent sample, as set forth above regarding claims 1 and 13. Elbadry further teaches processor-based analysis of optical sensor data (Elbadry, ¶¶[0116]-[0117]) and expressly identifies an absorption spectrum of components of effluent (Elbadry, ¶[0063]). However, Elbadry does not expressly state that its processor determines the amount of radiation absorbed by the effluent sample from the detected transmission signal.
Barat teaches a known optical detection and signal-processing implementation for quantitatively analyzing radiation received after irradiation of a fluid sample. Barat teaches an optical extinction measurement in which a collection fiber measures light loss resulting from absorption or scattering out of the detector field of view when material passes through the incident beam (Barat, p. 120, “Measurement principle”). Barat further teaches that the resulting photomultiplier signals are sampled at 120 kHz using a 16-bit A-D card and are captured and analyzed using Matlab and LabVIEW software (Barat, pp. 120-121, “Optical system”). Thus, Barat teaches detecting post-irradiation optical intensity changes, digitizing the detector output, and processor-based analysis of the resulting optical signal.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further configured Elbadry's optical absorption sensing system in view of Barat's detector-signal processing technique so that Elbadry's processor analyzes the detected optical transmission signal and determines the amount of radiation absorbed by the effluent sample. Elbadry expressly teaches optical absorption as a characteristic to be measured from drainage dialysate, expressly identifies an absorption spectrum of components of effluent, and teaches processor analysis of sensor outputs. Barat independently teaches a known implementation for digitizing and analyzing changes in detected optical radiation after the sample is irradiated. A person of ordinary skill would therefore have been motivated to apply Barat's demonstrated optical signal-acquisition and processing technique to Elbadry's expressly contemplated absorption measurement to obtain quantitative absorption information for use in Elbadry's patient-fluid analysis.
Barat is relied upon for the known acquisition and processor analysis of post-irradiation optical detector signals, not as an express teaching that Barat's extinction signal itself distinguishes the amount of absorbed radiation from the amount of scattered radiation. Elbadry continues to supply the absorption measurement being performed and the PD drainage-dialysate environment. The modification therefore applies a known optical signal-processing technique to the absorption sensing that Elbadry already expressly seeks to perform without changing Elbadry's fluid path or optical sensing principle.
Regarding claim 15, Elbadry teaches the optical system is further configured to measure an optical scattering caused by the effluent sample. Elbadry expressly teaches optical scatter sensing for monitoring PD drainage dialysate (Elbadry, ¶[0008]); a glass tube segment integrated with an optical scatter or absorption sensor (Elbadry, ¶[0124]); and that fluid characteristics including optical scatter may be measured in a non-fluid-contact manner (Elbadry, ¶[0127]).
Regarding claim 16, Elbadry does not fully teach the processor is configured to analyze the radiation after it irradiates the effluent sample and determine the amount of optical scattering caused by the effluent sample. Rather, Elbadry teaches the light source is configured to emit the beam of radiation that passes into the effluent sample and the photodetector is configured to receive radiation after it irradiates the effluent sample, as set forth above regarding claims 1 and 15, and Elbadry teaches processor analysis of the resulting sensor data (Elbadry, ¶¶[0116]-[0117]). However, Elbadry does not expressly teach the particular side-scatter collection and quantitative scattering analysis recited in claim 16.
Barat teaches a 532 nm light source that launches light across the channel and detection fibers coupled to photomultipliers (Barat, p. 120, “Optical system” and “Measurement principle”). Barat further teaches that the chip “was designed for two more collection fibres to be placed at 22 and 45 degrees” to measure side-scattered light and states that “[t]he data from these two collection fibres was qualitatively similar (for the beads)” such that only the light from the 45° fiber was thereafter collected and analyzed (Barat, p. 120, “Measurement principle”). Barat therefore establishes actual side-scatter information from the 22° and 45° collection arrangements and expressly analyzes the 45° side-scatter signal. Barat further teaches that the photomultiplier signals are sampled, digitized, captured, and analyzed using Matlab and LabVIEW (Barat, pp. 120-121, “Optical system”), and presents quantitative side-scatter measurements for characterization of particles (Barat, pp. 123-124, Figs. 5-6).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further configured Elbadry's optical scatter sensor in view of Barat to collect and process scattered radiation so as to determine an amount of optical scattering caused by the effluent sample. Elbadry expressly identifies optical scatter as a drainage-dialysate characteristic to be measured, while Barat teaches a known optical arrangement for collecting side-scattered light and processor-based analysis of the resulting detector signals. A person of ordinary skill would therefore have been motivated to apply Barat's quantitative scatter-detection technique to Elbadry's optical scatter measurement to obtain a numerical measure of the scattering characteristic already used by Elbadry for PD effluent monitoring. This modification concerns the optical collection and analysis technique and does not require adoption of Barat's microfluidic dimensions, hydrodynamic focusing, or particle-position discrimination.
Regarding claim 17, Elbadry further teaches the electrical system is further configured to measure at least one additional electrical property of the effluent sample. In addition to the Pal-derived capacitance measurement established regarding claim 1, Elbadry expressly teaches electrical conductivity sensing of PD drainage dialysate (Elbadry, ¶¶[0008]-[0009]) and electrical sensors including impedance and conductivity sensors associated with the tube carrying patient fluid (Elbadry, ¶[0124]). Conductivity is an additional electrical property beyond the capacitance measured according to Pal.
Claims 6-10 are rejected under 35 U.S.C. 103 as being unpatentable over Elbadry et al. (US 2019/0358387 A1), hereinafter Elbadry, and further in view of Barat et al. ("Simultaneous high speed optical and impedance analysis of single particles with a microfluidic cytometer," Lab on a Chip 12 (2012): 118-126), hereinafter Barat, and further in view of Pal et al. ("Void fraction measurement using concave capacitor based sensor: Analytical and experimental evaluation," Measurement 124 (2018): 81-90), hereinafter Pal, and further in view of Talebi et al. ("Analysis of impedance data from bubble flow in a glass/SU8 microfluidic device with on-channel sensors," Sensors and Actuators A: Physical 279 (2018): 543-552), hereinafter Talebi.
The modified Elbadry teaches claim 1 as described above.
Regarding claim 6, the combined Elbadry, Barat, and Pal does not fully teach that the thin film is a material that is both optically transparent and electrically conductive. Rather, Barat teaches the thin-film electrode construction established regarding claim 5, but its electrodes are platinum with a titanium seed layer and Barat expressly identifies optical obstruction caused by those electrodes in the optical interrogation region (Barat, p. 119, "System overview"; p. 121, "Integrated optics": "The two sharp dips in intensity occur because the impedance electrodes obscure the light in these regions").
Talebi teaches electrically conductive ITO electrodes fabricated on opposing Pyrex substrates of a fluid channel and expressly teaches that ITO is "an optically and UV-transparent conductive material" (Talebi, p. 545, §2.1). Talebi further identifies transparency as a device requirement "allowing full visual observation over the microchannel" while electrical impedance monitoring is performed (Talebi, p. 544, §2). Talebi teaches that approximately 700 nm of ITO is sputtered and the working electrodes are patterned by dry etching (Talebi, p. 545, §3.1.1). Thus, Talebi teaches an optically transparent and electrically conductive thin-film electrode material suitable for a fluid-containing sensing structure.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the combined Elbadry, Barat, and Pal in view of Talebi to form the thin-film electrode pairs using Talebi's optically transparent, electrically conductive ITO. Barat already provides thin-film electrodes on glass and expressly identifies the optical obstruction caused by its platinum electrodes, while Talebi teaches transparent ITO electrical sensing structures on glass specifically to preserve visual and optical access during electrical monitoring. Talebi therefore addresses the same optical-access problem expressly identified by Barat and is reasonably pertinent to solving that problem. A person of ordinary skill would have been motivated to replace Barat's opaque conductive electrode material with Talebi's transparent ITO while retaining the opposed electrode topology and Pal-derived capacitance measurement function. Barat and Talebi both fabricate conductive thin-film electrodes on glass-based substrates, and Talebi demonstrates successful electrical sensing with the transparent ITO construction, providing a reasonable expectation of success.
Regarding claim 7, as shown above regarding claim 6, the modified thin film is composed primarily of one of gold, In2O5Sn, or derivatives thereof. Talebi teaches indium tin oxide (ITO), an indium-tin-oxide composition that falls at least within the recited "In2O5Sn, or derivatives thereof" material class (Talebi, p. 545, §2.1; p. 545, §3.1.1). Thus, the Talebi material substitution already made regarding claim 6 provides the recited composition.
Regarding claim 8, the modified Elbadry further teaches a first surface of the at least two surfaces comprises the first pair of electrodes, which is a first optically transparent electrode pair, and wherein a second surface of the at least two surfaces comprises the second pair of electrodes, which is a second optically transparent electrode pair. As established regarding claims 1 and 2, Barat supplies the opposed upper and lower electrode-bearing surfaces and the two electrodes on the upper surface constitute the first pair while the two electrodes on the opposing lower surface constitute the second pair (Barat, p. 119, "Measurement principle"; Fig. 1(c); p. 122, discussion of Fig. 3). As established regarding claim 6, Talebi supplies the transparent, electrically conductive ITO material for those electrode pairs. Accordingly, the resulting first and second opposed sample-cell surfaces respectively comprise first and second optically transparent electrode pairs.
Regarding claim 9, the modified Elbadry does not expressly teach the light source is configured to emit the beam of radiation that passes through the first optically transparent electrode pair and into the effluent sample, and the photodetector is configured to receive the radiation after it irradiates the effluent sample and then passes through the second optically transparent electrode pair. Rather, the modified system includes Elbadry's transmission optical interrogation and opposed transparent electrode pairs as established above, but neither Elbadry nor the original Barat optical geometry expressly requires the transmission axis to pass successively through the first transparent pair, the fluid, and the second transparent pair.
Talebi teaches transparent ITO electrodes on opposing Pyrex substrates and expressly identifies transparency as permitting "full visual observation over the microchannel" while electrical impedance monitoring is performed (Talebi, pp. 544-545, §§2, 2.1; Fig. 1(b)). Thus, Talebi demonstrates that opposed electrical sensing structures can be made transparent specifically to preserve optical access through an electrically monitored fluid region.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the modified Elbadry by positioning Elbadry's light source and photodetector on opposite sides of the opposed transparent electrode-bearing surfaces so that the emitted beam passes through the first optically transparent electrode pair into the drainage dialysate and, after irradiating the dialysate, passes through the second optically transparent electrode pair before reaching the photodetector. Elbadry already teaches transmission optical interrogation through its fluid conduit, and Talebi teaches transparent opposed electrical sensing elements for preserving optical observation of the same electrically monitored fluid region. A person of ordinary skill would therefore have been motivated to use the transparent electrode-bearing surfaces for their expressly taught optical-access benefit, thereby obtaining co-located optical and electrical interrogation without electrode occlusion. The modification does not adopt or depend upon Barat's lateral microfluidic optical geometry. Barat is relied upon for the opposed electrode-pair topology, Talebi for the transparent electrode construction and optical access, and Elbadry for the transmission optical system in the PD drainage conduit.
Regarding claim 10, the modified Elbadry does not fully teach that the electrical system comprises a capacitor comprising two capacitor electrodes, wherein the first optically transparent electrode pair is a first capacitor electrode pair, and the second optically transparent electrode pair is a second capacitor electrode pair. As established regarding claim 1, Pal teaches two capacitance-measurement paths formed between an exciter group and a measuring group, and as established regarding claims 6-9, the respective groups are implemented as optically transparent opposed electrode pairs. However, the references have not yet expressly characterized the transparent opposed pair arrangement at the claim-pair level as first and second capacitor electrode pairs.
Pal expressly teaches four conduit-associated electrodes arranged to form two parallel-plate capacitors C_AC and C_BD, with A and B serving as exciter electrodes and C and D as measuring electrodes (Pal, p. 82, §§2.1-2.2). Talebi further teaches that "a parallel plate configuration across the channel yields a single integral signal corresponding to effective physical properties (i.e. permittivity and conductivity) of the composite media in the channel between the electrodes" (Talebi, p. 543, §1). Talebi therefore confirms that opposed transparent electrodes spanning a fluid region may function in a parallel-plate electrical configuration responsive to material between the electrodes.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have retained the capacitor-electrode function established by Pal when implementing the electrode pairs using Talebi's transparent ITO construction. The two electrodes of the first opposed surface would collectively serve as the first capacitor electrode pair and the two electrodes of the second opposed surface would collectively serve as the second capacitor electrode pair, with the corresponding excitation-to-measurement paths extending through the effluent. Pal demonstrates the capacitance-measurement function of the four-electrode arrangement, while Talebi demonstrates electrically functional transparent opposing electrodes and expressly teaches the parallel-plate sensitivity of such across-channel configurations. A person of ordinary skill would therefore have had a reasonable expectation that replacing the electrode material with transparent ITO would preserve the electrical capacitor function while enabling the optical path established regarding claim 9.
Claims 11 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Elbadry et al. (US 2019/0358387 A1), hereinafter Elbadry, and further in view of Barat et al. ("Simultaneous high speed optical and impedance analysis of single particles with a microfluidic cytometer," Lab on a Chip 12 (2012): 118-126), hereinafter Barat, and further in view of Pal et al. ("Void fraction measurement using concave capacitor based sensor: Analytical and experimental evaluation," Measurement 124 (2018): 81-90), hereinafter Pal, and further in view of Meyer et al. ("Mercury-Gold Minigrid Optically Transparent Thin-Layer Electrode," Analytical Chemistry 49(4) (1977): 602-605), hereinafter Meyer.
The modified Elbadry teaches claim 1 as described above.
Regarding claim 11, the combined Elbadry, Barat, and Pal does not fully teach that both the first pair of electrodes and second pair of electrodes comprise an optically transparent opening. Barat teaches the opposed first and second electrode-pair structure, but its electrodes are solid platinum thin films and Barat expressly states that the electrodes obscure the light in the optical interrogation region (Barat, p. 119, "System overview"; p. 121, "Integrated optics").
Meyer teaches optically transparent electrodes in which optical transmission is provided by physical openings in a conductive electrode. Meyer teaches that "[o]ptically transparent electrodes (OTEs) enable spectral monitoring of electrode processes during an electrochemical experiment by virtue of an optical beam passing through the electrode itself" (Meyer, p. 602). Meyer further teaches that "[a] second category of OTE is the minigrid electrode which consists of a metal (gold, nickel, silver, copper) grid with from 100 to 2000 wires per inch" and that "[i]n this case the transparency is due to the physical holes in the minigrid structure" (Meyer, p. 602). Thus, Meyer literally teaches a conductive electrode comprising optically transparent physical openings.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the modified Elbadry in view of Meyer to implement at least one electrode of each Barat-derived opposed electrode pair as an apertured metal minigrid in the optical interrogation region. Each electrode pair would thereby comprise an optically transparent opening through the physical holes of the minigrid electrode it comprises. Barat expressly identifies obstruction by its solid platinum electrodes as a problem, while Meyer teaches a known metal electrode construction whose purpose is to permit an optical beam to pass through the electrode itself. Meyer is therefore reasonably pertinent to the optical-access problem presented by Barat. A person of ordinary skill would have been motivated to substitute the apertured minigrid construction for the solid electrode material at the optical path to preserve electrical electrode functionality while providing literal optical openings.
A person of ordinary skill would have had a reasonable expectation of success because Meyer demonstrates optically transparent metal minigrid electrodes assembled into thin-layer electrochemical cells and reports substantial optical transmittance through the physical openings. The modification changes the local electrode construction used in the optical region, not the opposed-pair topology, the Elbadry drainage conduit, or the Pal-derived capacitance measurement principle.
Regarding claim 12, the modified Elbadry partially teaches the light source is configured to emit the beam of radiation that passes through a first optically transparent opening in the first pair of electrodes and into the effluent sample, and the photodetector is configured to receive the radiation after it irradiates the effluent sample and then passes through a second optically transparent opening in the second pair of electrodes. As established regarding claim 11, the opposed first and second electrode pairs each comprise a physical optically transparent minigrid opening. Elbadry teaches transmission optical interrogation through the effluent sample, but the modified system does not yet expressly arrange the optical axis through a first minigrid opening, the sample, and a second opposed minigrid opening.
Meyer expressly teaches optical interrogation "by virtue of an optical beam passing through the electrode itself" and teaches that minigrid transparency is due to physical holes in the electrode structure (Meyer, p. 602). Barat supplies the opposed electrode-pair placement, and Elbadry supplies the transmission optical system through the fluid-containing sensing region.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have aligned Elbadry's light source and photodetector with corresponding openings in the opposed Meyer-modified electrode pairs so that the emitted beam passes through a first physical opening in the first electrode pair, irradiates the drainage dialysate, and then passes through a second physical opening in the second electrode pair before reaching the photodetector. The motivation is the same optical-access benefit taught by Meyer and the same electrode-occlusion problem expressly identified by Barat. Aligning the transmission path with opposed transparent openings predictably uses those openings for their disclosed purpose while retaining Elbadry's existing transmission optical sensing. The modification does not require adopting Barat's lateral microfluidic optical arrangement. Barat supplies the opposed pair geometry, Meyer supplies the physical optical openings, and Elbadry supplies the transmission optical path through the PD effluent.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Elbadry et al. (US 2019/0358387 A1), hereinafter Elbadry, in view of Barat et al. (“Simultaneous high speed optical and impedance analysis of single particles with a microfluidic cytometer,” Lab on a Chip 12 (2012): 118-126), hereinafter Barat, and further in view of Pal et al. (“Void fraction measurement using concave capacitor based sensor: Analytical and experimental evaluation,” Measurement 124 (2018): 81-90), hereinafter Pal, and further in view of Nasir et al. (“Electrical detection of blood cells in urine,” Heliyon 6 (2020), e03102), hereinafter Nasir.
The modified Elbadry teaches claim 1 as described above.
Regarding claim 18, the modified Elbadry does not expressly teach that the processor is further configured to operate an algorithm configured to collectively process the optical signal and the capacitance signal to determine an amount of a compound in the effluent sample. As set forth regarding claim 1, the combined system generates and collectively processes optical and capacitance information to characterize the drainage dialysate, but does not expressly state that those particular signals are collectively processed to determine an amount of a compound.
The term “compound” is interpreted inclusively in light of the Specification and is not limited to a discrete chemical species. The Specification expressly identifies leukocytes, blood cells, biological materials, and derivatives thereof among examples of the recited compound. Accordingly, a determined leukocyte or white-blood-cell concentration constitutes an amount of a compound within the scope of claim 18 (Specification, ¶[0018]).
Elbadry expressly teaches processor-based determination of constituent amounts from multiple sensor modalities in dialysis fluid. Elbadry teaches estimating total-particle and leukocyte concentrations from optical-detector signal data, calculating glucose and salt concentrations from combined glucose-monitor and ionic-conductivity information, spectrometric monitoring of dialysate components, and analyte-concentration-dependent capacitance changes for creatinine sensing (Elbadry, ¶[0022], [0298], [0299], [0301]). Elbadry further states that multiple sensor data may be used concurrently to accurately determine monitoring metrics (Elbadry, ¶[0340]).
Barat teaches simultaneous acquisition and joint analysis of optical extinction, side-scatter, fluorescence, and electrical impedance measurements corresponding to the same particle events. Barat uses relationships between the optical and electrical measurements to characterize and distinguish particle populations (Barat, pp. 123-124, Figs. 5-6).
Nasir teaches label-free quantitative detection of red and white blood cells suspended in urine by measuring the capacitance of the biological-fluid suspension. Nasir explains that the inclusion of blood cells in a biological fluid alters its dielectric properties and investigates the effects of increasing RBC and WBC concentrations on capacitance measurements (Nasir, p. 3, §3). After correcting for the changing electrical background of the urine, Nasir obtains a stepwise increase in capacitance with increasing cell concentration and distinguishes concentrations as low as 100 cells/ml for both RBCs and WBCs (Nasir, p. 5, §5, Fig. 4). Nasir further extracts dielectric constants from the measured capacitance, generates calibration curves correlating the electrical measurements with RBC and WBC concentrations, and uses those curves to determine the number of cells in the biological-fluid sample (Nasir, pp. 5-8, §§5-7, Fig. 6).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further configured the processor of the modified Elbadry system in view of Nasir to use the optical signal and the Pal-derived capacitance signal as inputs to a common algorithm that determines a leukocyte concentration in the drainage dialysate. Elbadry already identifies quantitative leukocyte concentration as a monitoring objective and expressly teaches concurrently using multiple sensor data to improve the accuracy of a monitoring metric (Elbadry, ¶[0022], [0340]). Barat demonstrates that optical and electrical measurements provide jointly usable information for characterizing a particle population (Barat, pp. 123-124, Figs. 5-6). Nasir establishes the missing technical relationship by demonstrating that capacitance measurements of an aqueous biological-fluid suspension can be calibrated and processed to determine RBC and WBC concentrations (Nasir, pp. 5-8, §§5-7, Figs. 4, 6).
A person of ordinary skill therefore would have been motivated to apply Nasir’s background-correction and calibration technique to the capacitance signal already generated by the Pal-configured electrodes and to combine the resulting capacitance-dependent cell-concentration information with Elbadry’s optical signal in Elbadry’s existing multisensor algorithm. Doing so would provide two complementary measurements directed to the same leukocyte-containing particle population and thereby improve the accuracy and reliability of Elbadry’s leukocyte-concentration determination. Nasir is reasonably pertinent to this problem because it addresses quantitative detection of the same biological materials, including WBCs, in an aqueous excretory fluid using capacitance measurements.
One of ordinary skill would have had a reasonable expectation of success because the modified system already generates optical and capacitance signals from the same fluid sample, Elbadry already processes multiple sensor data to determine monitoring metrics, and Nasir demonstrates correction of the biological-fluid background followed by calibration of capacitance information to cell concentration. The modification concerns the processing and calibration of the existing capacitance signal and does not require replacing Pal’s four-electrode arrangement or altering the operating principle of the modified Elbadry system. The resulting processor collectively processes the optical signal and the capacitance signal to determine an amount of a compound, specifically a leukocyte concentration, in the effluent sample, as claimed.
Claims 19 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Elbadry et al. (US 2019/0358387 A1), hereinafter Elbadry, and further in view of Barat et al. ("Simultaneous high speed optical and impedance analysis of single particles with a microfluidic cytometer," Lab on a Chip 12 (2012): 118-126), hereinafter Barat, and further in view of Talebi et al. ("Analysis of impedance data from bubble flow in a glass/SU8 microfluidic device with on-channel sensors," Sensors and Actuators A: Physical 279 (2018): 543-552), hereinafter Talebi.
Regarding claim 19, Elbadry teaches a system for characterizing an effluent sample from a patient undergoing peritoneal dialysis (PD) (Elbadry, ¶¶[0008]-[0009], wherein for peritoneal dialysis patients a patient monitoring device connected to the dialysis catheter uses a combination of sensors, including optical scatter or absorption and electrical sensing, to monitor drainage dialysate and detect dialysis-related complications).
Elbadry further teaches a container for enclosing the effluent sample, wherein the container is configured such that all effluent from the patient flows through the container (Elbadry, ¶[0115]: the patient monitoring device "may be coupled in-line with a drainage line (D), such as to receive dialysate from the patient and pass it onto a drainage vessel"; Fig. 13; ¶[0121]: "the waste dialysate and fresh dialysate both flow through the same set of sensors"; ¶[0123]: in a drain-only variation, "a set of sensors is connected only to the waste dialysate solution port" and the patient monitoring device "monitors only the drainage dialysate solution", wherein the waste dialysate passes from the patient through the in-line monitoring conduit and sensing arrangement before proceeding along the drainage path).
Also, regarding claim 19, Elbadry does not fully teach an electrical system comprising a first pair of electrodes and a second pair of electrodes, with both the first pair of electrodes and second pair of electrodes comprising a portion that is optically transparent, attached directly to the container, and configured to measure an electrical property of the effluent sample. Rather, Elbadry teaches electrical sensing integrated with the fluid conduit, including a tube that integrates fluid-contacting sensors such as impedance and conductivity sensors (Elbadry, ¶[0124]). However, Elbadry does not teach first and second electrode pairs attached directly to opposing portions of the container, with both pairs configured to measure an electrical property and comprising optically transparent portions.
Barat teaches an impedance measurement region comprising four electrodes, including two electrodes fabricated on the upper channel surface and two electrodes fabricated on the lower channel surface (Barat, p. 119, "Measurement principle"; Fig. 1(c)). Figure 1(c) shows the two upper electrodes coupled to the electrical excitation source and the two lower electrodes coupled to the differential amplifier and data acquisition electronics. Barat further describes the lower electrodes as "the measurement electrodes" and the upper half of the channel as "connected to the source" (Barat, p. 122, discussion of Fig. 3). Accordingly, for purposes of the claimed arrangement, the two upper electrodes constitute a first pair on one channel surface and the two lower electrodes constitute a second pair on the opposing channel surface.
Barat further teaches that the electrodes are attached directly to the fluid-containing channel structure. Barat teaches platinum electrodes having a Ti seed layer fabricated directly on glass wafers, with the fluidic channel subsequently formed on the electrode-bearing wafers (Barat, p. 119, "System overview"). The glass wafers constitute the opposing substrates forming the fluid-containing channel. Accordingly, the electrodes are attached directly to the structural substrates forming opposing walls of the fluid-containing structure.
Barat teaches that the four electrodes together form "a differential measurement system" (Barat, p. 119, "Measurement principle"). Barat additionally teaches that "[a] sinusoidal voltage of 1 Vpp at 1 MHz was applied to both pairs of electrodes and the current measured using custom built electronics and a lock-in amplifier" (Barat, p. 121, "Impedance system"). Barat uses "pair" in that statement according to its designation of the opposed upper-and-lower electrode measurement locations. Consistent with that terminology, Fig. 1(c) shows electrical excitation delivered through the two upper electrodes and the resulting electrical response received through the two lower electrodes. Thus, all four electrodes are electrically active components of Barat's impedance measurement system. When those same four electrodes are grouped according to their disclosed channel surfaces for purposes of the presently claimed first and second pairs, the upper first pair provides the electrical excitation required for the measurement and the lower second pair receives the corresponding electrical response. Thus, both the first pair and the second pair are configured as operative components of the measurement of an electrical property of the fluid.
Barat does not teach that those electrode pairs comprise optically transparent portions. Rather, Barat teaches "metal electrodes consisting of 200 nm thick platinum with a 20 nm Ti seed layer" (Barat, p. 119, "System overview") and expressly identifies their interference with optical interrogation, stating that "the two sharp dips in intensity occur because the impedance electrodes obscure the light in these regions" (Barat, p. 121, "Integrated optics").
Talebi teaches electrically conductive ITO electrodes fabricated on opposing Pyrex substrates of a fluid-containing channel and expressly teaches that ITO is "an optically and UV-transparent conductive material" (Talebi, p. 545, §2.1). Talebi further teaches a device configured for "full visual observation over the microchannel" while impedance is measured between electrodes spanning the channel (Talebi, p. 544, §2). Talebi teaches that the device comprises Pyrex chips and SU8 passivation/structural layers and that the working and common-ground electrodes are passivated against direct fluid contact by an SU8 layer (Talebi, p. 545, §2.1; Fig. 1(b)). Talebi further teaches that the ITO electrodes are formed on the Pyrex substrates before the SU8 passivation is formed over the electrodes. Thus, Talebi's electrodes are attached directly to the Pyrex substrates forming the fluid-containing structure. The SU8 passivation layer lies between the electrode and the fluid, not between the electrode and the Pyrex substrate, and therefore does not affect the direct attachment of the electrode to the channel-forming substrate. Talebi therefore demonstrates an opposing, optically transparent electrode structure that electrically interrogates fluid while preserving optical access through the sensing region.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Elbadry in view of Barat and Talebi to implement Elbadry's expressly contemplated conduit-integrated electrical sensing using Barat's four-electrode architecture, with the two upper electrodes forming a first pair attached directly to one surface of the fluid-containing sensing region and the two lower electrodes forming a second pair attached directly to the opposing surface, and to fabricate the portions of those electrodes intersecting the optical interrogation region from Talebi's optically transparent, electrically conductive ITO. Elbadry expressly calls for electrical sensing of patient fluid in the conduit but leaves the electrode implementation open, while Barat teaches an opposed channel-surface electrode arrangement whose source and measurement electrodes cooperate to determine an electrical property of fluid in the sensing region and are directly attached to the channel-forming substrates. Barat itself identifies optical obstruction by its platinum electrodes, and Talebi teaches the corresponding solution of transparent ITO electrodes directly formed on opposing fluid-channel substrates so that electrical sensing can be retained while preserving optical observation. Talebi's SU8 passivation is disposed over the electrodes toward the fluid and does not introduce an intervening layer between the electrodes and the substrates to which they are attached. Talebi is therefore reasonably pertinent to the particular optical-access problem expressly identified by Barat. A person of ordinary skill would have been motivated to employ Talebi's transparent conductive material in the portions of Barat's electrode architecture intersecting the optical path to eliminate that obstruction while retaining the electrical sensing function.
The modification does not require retaining Barat's hydrodynamic focusing or its single-particle cytometry operating conditions. Those features are used by Barat for discrimination of individual particles and are not the teaching being applied to Elbadry. The modification applies Barat's opposed four-electrode electrical topology to Elbadry's already contemplated electrically monitored fluid conduit, while Talebi independently demonstrates that opposing transparent, passivated ITO electrodes directly attached to channel substrates can measure an electrical property of flowing fluid. Accordingly, the proposed modification does not depend upon preservation of Barat's particle-focusing principle of operation.
Also, regarding claim 19, the modified Elbadry does not fully teach an optical system comprising a light source and a photodetector, the light source configured to emit a beam of radiation that passes through the first pair of electrodes and irradiates the effluent sample, and the photodetector configured to detect the radiation after it irradiates the effluent sample and passes through the second pair of electrodes to generate an optical property of the effluent sample. Rather, Elbadry teaches an emitter configured to transmit light through patient fluid flowing through a fluid conduit and a detector configured to receive the transmitted light and generate signal data (Elbadry, ¶[0022]); teaches that "the fluid conduit comprises at least one transparent portion" (Elbadry, ¶[0023]); teaches optical sensing through a conduit portion transparent to ultraviolet, visible, or infrared radiation (Elbadry, ¶[0027]); and teaches a glass tube segment integrated with an optical scatter or absorption sensor (Elbadry, ¶[0124]). Further, the modified Elbadry includes first and second electrode pairs having optically transparent portions on opposing sides of the electrically monitored fluid region. However, the modified Elbadry does not expressly teach arranging the transmission optical path so that the emitted beam passes through the first electrode pair, through the effluent sample, and thereafter through the second electrode pair before reaching the photodetector.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the modified Elbadry by positioning Elbadry's light source and photodetector on opposite sides of the transparent electrode-bearing sensing region so that the emitted beam passes through the optically transparent portion of the first electrode pair, irradiates the drainage dialysate, and thereafter passes through the optically transparent portion of the second electrode pair before reaching the photodetector. Elbadry already teaches transmission optical interrogation through the patient fluid, Barat establishes that its electrical electrodes intersect the optical interrogation region and expressly identifies their optical obstruction as a problem, and Talebi teaches opposing transparent electrical sensing elements for preserving optical access to an electrically monitored fluid region. A person of ordinary skill would therefore have been motivated to direct Elbadry's transmission optical path through the transparent electrode-bearing surfaces so that the same effluent region can be interrogated optically and electrically without the electrode-induced occlusion identified by Barat. The modification would have constituted use of the transparent-electrode structure for its expressly taught optical-access benefit while retaining Elbadry's existing transmission optical sensing operation.
Also, regarding claim 19, the modified Elbadry does not fully teach a processor operating an algorithm configured to collectively process the optical property and the electrical property to characterize the effluent sample. Rather, Elbadry teaches that "a combination of different signals and/or signals over time are generated from the sensor array and reported or analyzed to determine patient status" (Elbadry, ¶[0004]) and further teaches a microcontroller that receives sensor outputs and may analyze sensor data and a server processor that may analyze transmitted patient-monitoring data (Elbadry, ¶¶[0116]-[0117]). However, Elbadry does not expressly teach collectively processing the particular optical property and electrical impedance property produced by the modified sensing systems.
Barat teaches simultaneous optical and electrical characterization and analysis of the resulting measurements. Barat presents optical extinction and side-scatter measurements in relation to impedance measurements for the same events and further presents side-scatter, fluorescence, and impedance measurements for characterization and discrimination of particle populations (Barat, pp. 123-124, Figs. 5-6).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the modified Elbadry by applying Barat's joint optical and electrical analysis to the optical and electrical properties measured from the drainage dialysate. Elbadry already teaches analyzing combinations of different sensor signals to determine patient status, while Barat teaches that optical and electrical properties provide complementary information when jointly used to characterize material in a fluid sample. A person of ordinary skill would therefore have been motivated to include the optical and electrical properties generated by the modified sensing systems in Elbadry's existing multisensor analysis so that both properties contribute to characterization of the PD effluent.
Regarding claim 20, Elbadry teaches a system for measuring leukocytes from an effluent sample from a patient undergoing peritoneal dialysis (PD) (Elbadry, ¶[0022]: an optical sensor arrangement transmits light through patient fluid flowing through a fluid conduit, generates signal data from the received light, and a controller may "estimate total particle concentration and leukocyte concentration using the signal data"; see also ¶¶[0008]-[0009], wherein multiple sensing modalities are used to monitor PD drainage dialysate for infection and other dialysis-related complications).
Elbadry further teaches a container for enclosing the effluent sample, wherein the container is configured such that all effluent from the patient flows through the container (Elbadry, ¶[0115]: the patient monitoring device may be coupled "in-line with a drainage line (D), such as to receive dialysate from the patient and pass it onto a drainage vessel"; Fig. 13; ¶[0121]: "the waste dialysate and fresh dialysate both flow through the same set of sensors"; ¶[0123]: in a drain-only variation, "a set of sensors is connected only to the waste dialysate solution port" and the patient monitoring device "monitors only the drainage dialysate solution", wherein waste dialysate passes from the patient through the in-line monitoring conduit and sensing arrangement before proceeding along the drainage path).
Also, regarding claim 20, Elbadry does not fully teach an electrical system comprising a first pair of electrodes and a second pair of electrodes, with both the first pair of electrodes and second pair of electrodes being optically transparent and attached directly to the container, with the first pair of electrodes configured to induce an electrical current into the effluent sample, and the second pair of electrodes configured to measure an electrical signal of the effluent sample that depends on the electrical current that is induced into the sample. Rather, Elbadry teaches electrical sensing integrated with the fluid conduit, including an impedance sensor associated with the conduit carrying the patient fluid (Elbadry, ¶[0124]). However, Elbadry does not teach optically transparent first and second electrode pairs attached directly to the conduit with the claimed excitation and measurement functions.
Barat teaches an impedance measurement region comprising four electrodes, including two upper electrodes connected to an electrical excitation source and two lower electrodes connected to differential measurement and data acquisition electronics (Barat, p. 119, "Measurement principle"; Fig. 1(c)). Barat expressly teaches that "AC voltages are applied to the upper two electrodes; when a cell passes between the electrodes the current is disturbed and this signal is measured using a lock-in amplifier, and processed to give the impedance" (Barat, p. 119, "Measurement principle"). Barat further describes the lower electrodes as "the measurement electrodes" and the upper half of the channel as "connected to the source" (Barat, p. 122, discussion of Fig. 3). Accordingly, for purposes of the claimed functional arrangement, the two upper electrodes constitute a first pair configured to induce electrical current into the fluid and the two lower electrodes constitute a second pair configured to measure the resulting current-dependent electrical signal.
Barat additionally states that "[a] sinusoidal voltage of 1 Vpp at 1 MHz was applied to both pairs of electrodes and the current measured using custom built electronics and a lock-in amplifier" (Barat, p. 121, "Impedance system"). Barat uses "pair" in that statement according to its own designation of each opposed upper-and-lower electrode measurement location. Figure 1(c) shows that electrical excitation at those locations is delivered through the two upper electrodes and that the resulting electrical response is taken through the two lower measurement electrodes. Thus, grouping the same four electrodes by disclosed channel surface and electrical function, with the upper electrodes constituting the claimed first pair and the lower electrodes constituting the claimed second pair, is consistent with Barat's disclosed wiring and operation.
Barat further teaches that the electrodes are attached directly to the fluid-containing channel structure. Barat teaches platinum electrodes having a Ti seed layer fabricated directly on glass wafers, with the fluidic channel subsequently formed on the electrode-bearing wafers (Barat, p. 119, "System overview"). The glass wafers constitute the opposing substrates forming the fluid-containing channel. Accordingly, Barat's source and measurement electrodes are attached directly to the structural substrates forming opposing walls of the fluid-containing structure.
Barat does not teach that those source and measurement electrodes are optically transparent. Rather, Barat teaches platinum electrodes having a Ti seed layer and expressly identifies optical obstruction caused by those electrodes in the optical interrogation region (Barat, p. 119, "System overview"; p. 121, "Integrated optics").
Talebi teaches optically transparent, electrically conductive ITO electrodes fabricated on opposing Pyrex substrates of a fluid channel, with the fluid positioned between the opposing electrode-bearing structures (Talebi, Fig. 1(b); pp. 544-545, §§2, 2.1). Talebi expressly teaches ITO on both Pyrex chips, identifies ITO as optically and UV-transparent, and teaches preservation of full visual observation of the microchannel while electrical impedance monitoring is performed. Talebi further teaches that the ITO electrodes are formed on the Pyrex substrates before SU8 passivation is formed over the electrodes. Thus, Talebi's ITO electrodes are attached directly to the Pyrex substrates forming the fluid-containing structure. The SU8 passivation separates the electrodes from direct fluid contact but lies on the fluid-facing side of the electrodes, not between the electrodes and the Pyrex substrates, and therefore does not affect their direct attachment to the channel-forming structure. Talebi thereby demonstrates electrical sensing of fluid through a transparent, electrically insulated electrode structure whose electrodes remain attached directly to the supporting channel substrates.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Elbadry in view of Barat and Talebi to implement Elbadry's expressly contemplated conduit-integrated electrical sensing using Barat's source-and-measurement electrode architecture, with the upper source electrodes forming the first pair attached directly to one surface of the fluid sensing region and the lower measurement electrodes forming the second pair attached directly to the opposing surface, and to fabricate those electrodes from Talebi's optically transparent, electrically conductive ITO. Elbadry expressly calls for electrical sensing of patient fluid in its conduit but leaves the electrode implementation open, while Barat teaches a known arrangement in which source electrodes apply AC electrical excitation and measurement electrodes receive the corresponding current-dependent electrical response and are attached directly to channel-forming substrates. Barat additionally identifies optical obstruction by its platinum electrodes, while Talebi teaches transparent ITO electrical sensing structures directly formed on opposing Pyrex channel substrates and specifically permitting simultaneous electrical monitoring and optical observation. Talebi's SU8 passivation lies over the electrodes toward the fluid rather than between the electrodes and the substrates to which they are attached, and therefore does not affect direct attachment of the electrodes to the fluid-containing structure. Talebi therefore addresses the same optical-access problem identified by Barat and is reasonably pertinent to solving that problem. A person of ordinary skill would have been motivated to replace Barat's opaque conductive electrode material with Talebi's transparent ITO while retaining Barat's disclosed source and measurement functions.
The modification does not require preservation of Barat's hydrodynamic focusing or single-particle cytometry operation. Claim 20 requires electrical excitation and measurement of the effluent, not Barat's particular particle-position discrimination technique. Barat is relied upon for the source-and-measurement electrode topology, Elbadry already calls for electrical sensing of fluid in its conduit, and Talebi independently demonstrates AC impedance measurement through opposed transparent electrodes directly attached to channel substrates without relying on Barat's hydrodynamic focusing. The proposed modification therefore retains the electrical sensing principle relevant to the claim without depending upon the cytometric operating conditions peculiar to Barat.
Also, regarding claim 20, the modified Elbadry does not fully teach an optical system comprising a light source and a photodetector, the light source configured to emit a beam of radiation that passes through one of the first pair of electrodes or second pair of electrodes and irradiates the effluent sample, and the photodetector configured to detect the radiation after it irradiates the effluent sample and passes through one of the first pair of electrodes and second pair of electrodes to generate an optical signal. Rather, Elbadry teaches an emitter configured to transmit light through patient fluid flowing through the fluid conduit and a detector configured to receive the transmitted light and generate signal data (Elbadry, ¶[0022]); teaches that the fluid conduit includes at least one transparent portion (Elbadry, ¶[0023]); teaches optical sensing through a conduit portion transparent to ultraviolet, visible, or infrared radiation (Elbadry, ¶[0027]); and teaches a glass tube segment integrated with an optical scatter or absorption sensor (Elbadry, ¶[0124]). Further, the modified Elbadry includes optically transparent source and measurement electrode pairs on opposing portions of the electrically monitored fluid region. However, the modified Elbadry does not expressly teach arranging the transmission optical path to pass through the recited electrode structures before and after irradiating the effluent sample.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the modified Elbadry by positioning Elbadry's light source and photodetector on opposite sides of the transparent electrode-bearing sensing region so that the emitted beam passes through an optically transparent electrode of the first pair or second pair before irradiating the drainage dialysate and, after traversing the drainage dialysate, passes through an optically transparent electrode on the opposing side before reaching the photodetector. Elbadry already teaches transmission optical interrogation of patient fluid through its conduit, Barat expressly identifies electrical-electrode obstruction of the optical measurement as a problem, and Talebi teaches opposing transparent electrical sensing elements for preserving optical observation of an electrically monitored fluid region. A person of ordinary skill would therefore have been motivated to direct Elbadry's transmission optical path through the transparent electrode-bearing region so that optical and electrical measurements can be obtained from the same portion of the effluent without the electrode-induced occlusion identified by Barat.
Also, regarding claim 20, the modified Elbadry does not fully teach a processor operating an algorithm configured to collectively process the optical signal and the electrical signal to characterize the effluent sample. Rather, Elbadry teaches that "a combination of different signals and/or signals over time are generated from the sensor array and reported or analyzed to determine patient status" (Elbadry, ¶[0004]) and further teaches a microcontroller and server processor configured to receive and analyze sensor data (Elbadry, ¶¶[0116]-[0117]). However, Elbadry does not expressly teach collectively processing the particular optical signal and electrical impedance signal generated by the modified sensing systems.
Barat teaches simultaneous acquisition and analysis of optical and electrical signals. Barat presents optical extinction and side-scatter measurements in relation to impedance for the same events and further uses side-scatter, fluorescence, and impedance measurements to characterize and distinguish particle populations (Barat, pp. 123-124, Figs. 5-6).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the modified Elbadry by applying Barat's joint optical and electrical analysis to the optical and electrical signals measured from the drainage dialysate. Elbadry already seeks to estimate leukocyte concentration, teaches optical and electrical monitoring of PD drainage fluid, and teaches analyzing combinations of sensor signals to determine patient status. Barat demonstrates that jointly analyzed optical and impedance measurements provide complementary information for characterizing particles. A person of ordinary skill would therefore have been motivated to include the optical and electrical signals produced by the modified sensing systems in Elbadry's existing multisensor analysis so that both sensing modalities contribute to characterization of the effluent and its leukocyte-containing particle population.
Response to Arguments
Examiner Interview Summary
Applicant's statements filed 5/4/2026, pages 7-8, regarding the Examiner Interview conducted on April 30, 2026 have been fully considered.
Applicant's Argument: Applicant states that during the Examiner Interview, the parties discussed two potential claim amendments directed to overcoming the then-current prior art rejections and that “the parties agreed that the amendments which are mirrored herein would likely overcome the current combinations of references, but that further search and consideration would be necessary.”
Examiner's Response: Applicant's statement regarding the Examiner Interview is accurate. As Applicant's own statement reflects, the discussion concerned whether the proposed amendments would likely overcome the then-current combinations of references and was expressly conditioned on further search and consideration. The amendments entered by Applicant are acknowledged as addressing the then-current grounds of rejection, and those grounds are not maintained in the present action.
Consistent with the condition expressly identified in Applicant's Interview Summary, further search and consideration were conducted. That further consideration resulted in the additional application of Pal, Talebi, and Meyer and in revised grounds of rejection that differ materially from the grounds discussed during the interview. Although Barat and Elbadry remain among the references applied in the present action, the present grounds do not maintain the prior allocation of teachings challenged by Applicant. In particular, the previous rejection relied on Barat's sealed microfluidic structure in addressing the container limitation. In the present grounds, Elbadry instead supplies the in-line PD drainage conduit through which the drainage effluent flows, while Barat is relied upon for selected electrode-structure and sensing teachings. Pal, Talebi, and Meyer are further applied for the additional teachings identified in the respective grounds of rejection.
Accordingly, the present action is consistent with the substance of the interview as recorded by Applicant. The amendments were considered with respect to the then-current combinations, those prior grounds are not maintained, and the further search and consideration expressly contemplated during the interview resulted in the revised grounds of rejection set forth in the present action.
35 U.S.C. 103 Rejection of Claims 1-5 and 13-18
Applicant's arguments filed 5/4/2026, page 8, regarding the previous rejection of claims 1-5 and 13-18 under 35 U.S.C. 103 over Barat in view of Elbadry have been fully considered but are moot because that ground of rejection is not maintained in the present action. The previous rejection of claims 1-5 and 13-18 is superseded by the present rejection of claims 1-5 and 13-17 under 35 U.S.C. 103 over Elbadry in view of Barat and further in view of Pal and claim 18 under 35 U.S.C. 103 over Elbadry in view of Barat and further in view of Pal. And further in view of Nasir. To the extent the underlying arguments concerning Barat's microfluidic structure, the combination of Barat with Elbadry, and the operation of the optical and electrical sensing systems remain applicable to the present ground, those arguments are addressed below.
Applicant's Argument: Applicant argues that amended claim 1 now recites "a container for enclosing the effluent sample, wherein the container is configured such that all effluent from the patient flows through the container." Applicant argues that the previous rejection relied on the sealed microfluidic structures of Barat as the claimed container and that Barat in view of Elbadry fails to disclose, teach, or suggest a container through which all effluent from the patient flows and in which the optical and electrical systems act upon the effluent sample. Applicant requests withdrawal of the rejection of claims 1-5 and 13-18 over Barat in view of Elbadry.
Examiner's Response: The argument is moot with respect to the previous rejection over Barat in view of Elbadry because that ground of rejection is not maintained in the present action. To the extent Applicant's argument regarding Barat's microfluidic structure and its combination with Elbadry remains relevant to the present rejection, the argument is not persuasive.
The present rejection does not rely on Barat's sealed microfluidic structure as the claimed container and does not require Barat's microfluidic channel to receive the entire volume of PD drainage effluent. Rather, Elbadry is relied upon for the claimed container and PD drainage flow path. Elbadry teaches a patient monitoring device coupled in-line with a drainage line to receive dialysate from the patient and pass it to a drainage vessel, teaches that waste dialysate flows through the same set of sensors, and teaches a drain-only configuration in which the sensor arrangement is connected to the waste dialysate solution port and monitors the drainage dialysate solution. Elbadry, ¶¶ [0115], [0121], [0123]. Thus, in the presently rejected system, the drainage dialysate passes from the patient through Elbadry's in-line monitoring conduit and sensing arrangement before proceeding along the drainage path.
Elbadry further teaches optical sensing of patient fluid flowing through the fluid conduit and electrical sensing associated with that conduit. Elbadry, ¶¶[0022]-[0027], [0124]. Barat is relied upon for the more limited teaching of a known four-electrode arrangement in which electrically active electrodes are disposed on opposing channel-forming surfaces and cooperate to electrically interrogate fluid occupying the intervening sensing region. The present rejection applies Barat's opposed electrode topology to the electrical sensing already contemplated by Elbadry. The rejection does not substitute Barat's microfluidic cytometer for Elbadry's drainage conduit and does not require adoption of Barat's channel dimensions, hydrodynamic focusing, example flow conditions, or particle-position discrimination.
Accordingly, to the extent Applicant's previous arguments concerning the dimensions, flow rate, or operating conditions of Barat's microfluidic cytometer are incorporated into the present remarks, those arguments do not address the modification presently proposed. The PD effluent continues to flow through Elbadry's drainage conduit, while Barat supplies the structural arrangement of electrically active electrodes associated with opposing portions of the fluid-containing sensing region.
The present rejection further relies on Pal for the capacitance-measurement operation recited by claim 1. Pal teaches four electrodes associated with a fluid-containing pipe, including two exciter electrodes and two measuring electrodes arranged to establish two capacitance-measurement paths responsive to material occupying the pipe. Pal further teaches use of its capacitance sensor with conductive and non-conductive liquids and experimentally demonstrates the technique using a 94 mm internal-diameter acrylic pipe. Thus, the capacitance technique applied in the present rejection is independently demonstrated in a fluid-conduit environment and does not depend upon Barat's micrometer-scale channel dimensions or hydrodynamic focusing.
Elbadry itself additionally recognizes capacitance-responsive sensing as useful for obtaining information concerning dialysis fluid and teaches collective analysis of different sensor outputs, including combinations of optical and electrical measurements, to determine patient status. Elbadry, ¶¶[0004], [0008]-[0009], [0298]. Barat further demonstrates simultaneous acquisition and analysis of optical and electrical measurements from a common fluid sensing region. Accordingly, once the Barat-derived electrode arrangement is configured according to Pal to obtain capacitance information from the drainage dialysate, the present rejection provides a reason to include that capacitance signal with Elbadry's optical signal in Elbadry's existing multisensor analysis.
Therefore, Applicant's argument concerning the previously rejected Barat/Elbadry system is moot as to that previous ground. To the extent the underlying argument is directed to the continued use of Barat with Elbadry, it does not establish error in the present rejection because Elbadry, rather than Barat, supplies the claimed all-effluent drainage container and flow path, while Barat supplies the opposed electrode topology and Pal supplies the capacitance-measurement technique.
Applicant has not presented separate substantive arguments directed to the additional limitations of dependent claims 2-5 and 13-18 apart from asserting their patentability based on the alleged deficiency of independent claim 1. Those additional limitations are addressed by the references and reasoning set forth in the present rejection above. Accordingly, the rejection of claims 1-5 and 13-18 under 35 U.S.C. 103 over Elbadry in view of Barat and further in view of Pal remain rejected under the present ground.
35 U.S.C. 103 Rejection of Claims 6-12, 19, and 20
Applicant's arguments filed 5/4/2026, pages 8-9, regarding the previous rejection of claims 6-12, 19, and 20 under 35 U.S.C. 103 over Barat in view of Elbadry and further in view of Choi have been fully considered but are moot because that ground of rejection is not maintained in the present action. The previous rejection is superseded by the present rejections of claims 6-10 under 35 U.S.C. 103 over Elbadry in view of Barat, Pal, and Talebi; claims 11 and 12 under 35 U.S.C. 103 over Elbadry in view of Barat, Pal, and Meyer; and claims 19 and 20 under 35 U.S.C. 103 over Elbadry in view of Barat and Talebi. Choi is not relied upon in any present ground of rejection. To the extent the underlying arguments concerning Barat's microfluidic structure, the combination of Barat with Elbadry, and the reason for providing optically transparent electrode structures remain applicable to the present grounds, those arguments are addressed below.
Applicant's Argument: Applicant argues that a skilled artisan would not have combined Barat and Elbadry to arrive at the claimed subject matter, that claims 19 and 20 contain subject matter analogous to amended claim 1, and that Choi fails to remedy the alleged deficiencies of Barat and Elbadry. Applicant further argues that Choi is merely relied upon for optically transparent electrodes and provides no motivation to modify Barat and/or Elbadry to arrive at the presently claimed systems.
Examiner's Response: The argument is moot with respect to the previous rejection over Barat in view of Elbadry and Choi because that ground of rejection is not maintained in the present action. Choi is not relied upon in any of the presently applied grounds. To the extent Applicant's arguments concerning the combination of Barat and Elbadry remain relevant to the present rejections, the arguments are not persuasive.
As discussed above, the present rejections do not require Barat's microfluidic cytometer to serve as the PD drainage container or require Elbadry's PD effluent to be processed according to Barat's particular microfluidic operating conditions. Elbadry supplies the PD drainage conduit, patient-fluid monitoring context, optical sensing, and electrical sensing context, while Barat supplies selected electrode structures and electrical sensing teachings as set forth in the respective rejections.
Regarding claims 6-10, the present rejection relies on Talebi, rather than Choi, for an optically transparent and electrically conductive thin-film electrode construction. Barat expressly identifies an optical-access problem with its platinum electrodes, stating that the impedance electrodes obscure the light in portions of the optical interrogation region. Talebi teaches electrically conductive ITO electrodes fabricated on opposing Pyrex substrates and expressly identifies ITO as an optically and UV-transparent conductive material. Talebi further teaches preservation of full visual observation over the microchannel while electrical impedance monitoring is performed.
Thus, unlike the previous argument addressed to Choi, the motivation in the present rejection is expressly tied to a problem identified in Barat itself. Barat supplies an electrically functional opposed thin-film electrode architecture but identifies optical obstruction caused by its electrode material. Talebi teaches transparent conductive ITO electrical sensing structures on glass specifically to preserve optical access during electrical monitoring. A person of ordinary skill therefore would have had reason to use Talebi's transparent ITO construction when implementing Barat's electrode arrangement in Elbadry's optically interrogated sensing region so as to retain electrical sensing while avoiding the electrode-induced optical obstruction identified by Barat.
Regarding claims 11 and 12, the present rejection likewise does not rely on Choi. Meyer is relied upon for the specifically recited "optically transparent opening." Meyer teaches metal minigrid electrodes in which optical transparency results from physical holes in the conductive electrode structure and expressly teaches optical interrogation by an optical beam passing through the electrode itself. Thus, the present rejection does not interpret a merely transparent conductive material as the claimed opening. Rather, Meyer supplies a conductive electrode having physical openings through which the optical beam may pass. Barat supplies the opposed electrode-pair arrangement, Meyer supplies the physical optical openings, and Elbadry supplies the transmission optical interrogation through the PD effluent.
Applicant's statement that claims 19 and 20 contain subject matter analogous to claim 1 also does not establish error in the present rejections of those claims. As with claim 1, Elbadry is relied upon for the container through which the PD drainage effluent flows. The present rejections do not rely upon Barat's microfluidic channel as the all-effluent container.
Regarding claim 19, Barat supplies an opposed four-electrode architecture in which the electrodes are directly attached to the channel-forming substrates and cooperate to measure an electrical property of fluid in the sensing region. Talebi supplies transparent conductive ITO electrode portions directly formed on opposing channel substrates. Elbadry supplies the transmission optical interrogation of the PD drainage fluid. Barat's express identification of optical obstruction and Talebi's teaching of transparent electrical sensing structures provide the reason for directing Elbadry's transmission optical path through the transparent electrode-bearing region.
Regarding claim 20, Barat further expressly teaches upper source electrodes to which AC electrical excitation is applied and lower measurement electrodes that receive the resulting current-dependent electrical response. Talebi supplies the optically transparent conductive construction for those electrodes, while Elbadry supplies the all-effluent PD drainage conduit and transmission optical sensing. Accordingly, the present rejection addresses the separately recited excitation and measurement functions of claim 20 without requiring Barat's hydrodynamic focusing or single-particle cytometry operating conditions.
The present rejections of claims 19 and 20 also do not rely merely on the physical ability to place transparent electrodes in an optical path. Barat itself identifies electrode-induced optical obstruction, Talebi expressly teaches transparent electrical sensing structures to preserve optical observation during electrical monitoring, and Elbadry already teaches transmission optical interrogation and electrical monitoring of patient fluid. The motivation for the modifications therefore arises from the teachings of the references and the optical-access problem expressly identified in the prior art.
Accordingly, Applicant's arguments concerning the previous rejection over Barat, Elbadry, and Choi are moot because that ground is not maintained. To the extent the underlying arguments concerning Barat's microfluidic operating conditions, the combination of Barat with Elbadry, and the reason for employing optically transparent electrode structures remain applicable to the present grounds, those arguments are not persuasive for the reasons discussed above.
Applicant has not presented separate substantive arguments directed to the additional limitations of dependent claims 6-12 apart from the arguments addressed above. Accordingly, the present rejections of claims 6-10 under 35 U.S.C. 103 over Elbadry in view of Barat, Pal, and Talebi; claims 11 and 12 under 35 U.S.C. 103 over Elbadry in view of Barat, Pal, and Meyer; and claims 19 and 20 under 35 U.S.C. 103 over Elbadry in view of Barat and Talebi remain rejected under the present ground.
Conclusion
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/AARON MERRIAM/Examiner, Art Unit 3791
/MATTHEW KREMER/Primary Examiner, Art Unit 3791
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