DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 07/31/2025 has been entered.
Status of Claims
Claims 1, 6-8, 10-11, 18, 21-23, 25, 28, 77-82 are pending. Claim 1 has been amended. Claims 81-82 have been newly added.
Claims 1, 6-8, 10-11, 18, 21-23, 25, 28, 77-82 are under examination.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1, 6-8, 10-11, and 80-82 are rejected under 35 U.S.C. 103 as being unpatentable
over Edson et al., (WO 2016/175985 A1; published on 11/03/2016; effectively filed on
04/04/2016) (IDS filed on 05/24/2021), and in view of Rahman et al., (US 2015/0118728
A1; published on 04/30/1015; effectively filed on 04/19/2013) (IDS filed on 05/24/2021).
Regarding claim 1, Edson teaches a method for sampling microplastics (see [0005] “In particular embodiments, methods and systems are provided which pertain to the automation of
microplastic particle sampling, with the potential to provide autonomous sampling for days,
weeks or even months at sea without the need for human intervention and costly time on
research vessels.”).
Edson teaches contacting a liquid sample with a filter and using filters to collect the microplastics (see [0006] “In certain aspects, the present disclosure pertains to automated systems for sampling particles in a water sample from a body of water over a sampling period. These systems may comprise: (a) a power supply; (b) a fluid intake path configured to receive a stream of sample water from the body of water as a result of an action of one or more pumps; (c) a detection system configured to detect particles in the stream of sample water; (d) a first fluid return path that is configured to receive and return the sample water to the body of water; (e) a second fluid return path comprising a first particle filter that is configured to receive the stream of sample water, pass the stream of sample water through the first particle filter, and return the sample water to the body of water; (f) a controller that is configured to (i) direct the stream of sample water along the first fluid return path until one or more particles are detected, (ii) in the event of detection of one or more particles by the detection system, direct the stream of sample water along the second fluid return path for a predetermined period, (ii) after the predetermined period, redirect the stream of sample water along the first fluid return path.”). Edson teaches that sampling methods include analyzing the microplastic particles that are collected, and calculating the plastic concentration based on the volume of water that was sieved through the net during the sample time (see [0003]).
Edson is silent towards the use of microslit filters.
Rahman teaches a method (see abstract, “a method for separating a biological entity from a sample volume is also provided”) comprising:
contacting a liquid sample suspected of having one or more microparticle(s) with a microslit filter (see [0239]-[0241] Figs. 11A-11B apparatus and method for circulating tumor cells (CTCs) isolation from whole blood…white blood cells (WBCs) within the sample were depleted by immunomagnetic separation before being flowed down to the chip 900 to retain CTCs, see [0223] “A micro slit membrane was designed to deplete platelets, RBCs, smaller-sized WBCs, such as lymphocytes, monocytes, and granulocytes that escaped immunomagnetic depletion, while retaining the majority of the other nucleated cells”, see [0242] “The microfiltration process of 4-ml blood assay was completed in less than 5 minutes. Approximately 2 mL of 1. PBS was introduced and flowed continuously to wash and remove the remaining RBCs on the micro slit membrane 800 in the microfluidic chamber 904.”) comprising
a plurality of openings, wherein the openings are cubic prisms, rectangular prisms, or trapezoids (see fig. 8, fig, 18c, [0223] “Compared to commonly used circular/hexagonal microfilters openings, the rectangular slit design has the advantage of defraying the pressure applied across the cells trapped on the membrane and preserving the viability and morphology of target cells.”) have a width from 0.5µm to 15µm and a length from 5µm to 100µm ([0223] “The membrane includes periodically arranged precise slits with a slit dimension of approximately 5.5-µm in width and 40- µm in length.”) and
have an aspect ratio from 1:0.33 to 1:200 (instant applications specification
teaches that the aspect ratio is in terms of width to length, and that the aspect ratio would be
determined by dividing the length by the width [0108]. The aspect ratio for Rahman is (40/5.5)=
1:7.27) and
the microslit filter has a thickness from 50 nm to 25µm, a porosity from 1% to 75%
(see [0285] “The membrane 1800 has an active diameter of about 21 mm, as represented within the dotted circle 1802, and a thickness of about 10µm, and containing slits, as represented by 1804 for some slits, with slit dimension approximately 5.5x40 µm, and a fill factor of approximately 39%.”), and
optionally washing the one or more retained particle(s) (see [0242] The microfiltration
process of 4-ml blood assay was completed in less than 5 minutes. Approximately 2 mL of 1.
PBS was introduced and flowed continuously to wash and remove the remaining RBCs on the
micro slit membrane 800 in the microfluidic chamber 904. Fixation of cells followed by the
staining protocol was initiated after the washing step.”), and
subsequentially measuring the quantity of the one or more retained microparticles directly on the microslit filter to determine the concentration of the one or more microparticles present in the liquid sample (see [0256] “Next, various concentrations of cell lines were spiked in 2-mL of whole blood and processed through the cell isolation system 1140 (FIG. 11B). The isolated cancer cells and other nucleated cells were retained on the micro slit membrane 800 after the microfiltration process. The isolated target cells were fixed and stained according to the above-described staining protocol for CTC identification and counting”, see [0244] “Cell counting and image capturing were performed using a 40x objective lens.”),
wherein measuring the quantity of the one or more retained microplastic particle(s) comprises optical imaging, electronic interrogation, optical diffraction, transmembrane pressure, or a combination thereof (see [0256] “The isolated target cells were fixed and stained according to the above-described staining protocol for CTC identification and counting.”, see [0244] “Cell counting and image capturing were performed using a 40x objective lens.”).
It would have been prima facia obvious, at the time of the instant application, to use the plastic microparticles of Edson with the methods of filtering microparticles with a microslit filter taught by Rahman. Rahman demonstrates the usefulness of using microslit filters for microparticles such as the microplastic particles taught by Edson.
Regarding claim 6, Edson teaches wherein the liquid sample comprises a food, an environmental sample, or an industrial sample (see [0013] “In other aspects, the present disclosure pertains to methods for sampling particles in a water sample from a body of water over a sampling period using an automated system. The methods may comprise: (a) drawing a stream of sample water from a body of water and passing the stream of sample water through a particle detector that analyzes the stream of sample water for the presence or absence of particles; (b) directing the stream of sample water along a first fluid return path through which the stream of sample water flows and is returned to the body of water until such time that particles are detected; (c) in the event particles are detected, directing the stream of sample water for a predetermined period along a second fluid return path comprising a first particle filter through which sample water flows after which it is returned to the body of water; (d) after the
predetermined time period has elapsed, redirecting the stream of sample water along the first
fluid return path; and (e) performing steps (b)-(d) until such time that the sampling period is
complete, at which point the system ceases drawing a stream of sample water from the body of
water.”).
Regarding claim 8, Edson teaches wherein contacting a liquid sample with a filter includes pumping (see [0006] “In certain aspects, the present disclosure pertains to automated
systems for sampling particles in a water sample from a body of water over a sampling period.
These systems may comprise: (a) a power supply; (b) a fluid intake path configured to receive a
stream of sample water from the body of water as a result of an action of one or more pumps;
(c) a detection system configured to detect particles in the stream of sample water; (d) a first
fluid return path that is configured to receive and return the sample water to the body of water;
(e) a second fluid return path comprising a first particle filter that is configured to receive the
stream of sample water, pass the stream of sample water through the first particle filter, and
return the sample water to the body of water; (f) a controller that is configured to (i) direct the
stream of sample water along the first fluid return path until one or more particles are detected,
(ii) in the event of detection of one or more particles by the detection system, direct the stream of sample water along the second fluid return path for a predetermined period, (ii) after the
predetermined period, redirect the stream of sample water along the first fluid return path.”
Edson is silent towards the use of a microslit filter.
Rahman teaches wherein the contacting a liquid sample with a microslit filter, includes
gravity flow, hydrostatic pressure, pumping, vacuum, centrifugation, gas pressurization, or
tangential flow (see [0241] “the WBC-depleted assay was driven by a constant 3.5-mBar air
pressure (e.g. pump 1150; MV20 pump, Ibidi) through the microfluidic chip 900 for microfiltration
process. The applied pressure by the pump 1150 was monitored in real time by pump controller
software.”, see [0240] “the WBC-depleted blood was flowed through the chip setup 900
undergravity.”, see [0292] “Blood sample 1901 was flown with a constant air pressure source, e.g. pump 1952 (MV20 pump, Ibidi) controlled by manufacturer's software. The pressure source
1952 was measured by a calibrated external pressure gauge (Catalog#717-100G, Fluke) 1956.
In addition, the applied pressure was monitored in real time by the manufacturer's software. The
sample 1901 was contained in a 5-ml syringe barrel (Catlog#302135, BD) 1902 that is
connected to the membrane holder 1962 via the luer connection 1960. The micro slit membrane
1964 was supported by a mesh-like structure within the holder 1962 to prevent buckling of the
membrane 1964 under fluid pressure.”).
Regarding claim 80, Edson teaches wherein the detection of the one or more captured
microplastic particles detects one or more physical property of the one or more microplastic
particles (see [0012] “In certain embodiments, which can be employed in conjunction with any of the above aspects and embodiments, the system may be configured to detect particles that are larger than 0.5 mm diameter and smaller than 8 mm in diameter.”, see [0036] “Particles flowing through the system can be detected and grouped into a relative size category using this
system.”).
Regarding claim 81, Edson teaches a method for sampling microplastics (see [0005] “In particular embodiments, methods and systems are provided which pertain to the automation of microplastic particle sampling, with the potential to provide autonomous sampling for days, weeks or even months at sea without the need for human intervention and costly time on research vessels.”).
Edson teaches contacting a liquid sample with a filter and using filters to collect the microplastics (see [0006] “In certain aspects, the present disclosure pertains to automated systems for sampling particles in a water sample from a body of water over a sampling period. These systems may comprise: (a) a power supply; (b) a fluid intake path configured to receive a stream of sample water from the body of water as a result of an action of one or more pumps; (c) a detection system configured to detect particles in the stream of sample water; (d) a first fluid return path that is configured to receive and return the sample water to the body of water; (e) a second fluid return path comprising a first particle filter that is configured to receive the stream of sample water, pass the stream of sample water through the first particle filter, and return the sample water to the body of water; (f) a controller that is configured to (i) direct the stream of sample water along the first fluid return path until one or more particles are detected, (ii) in the event of detection of one or more particles by the detection system, direct the stream of sample water along the second fluid return path for a predetermined period, (ii) after the predetermined period, redirect the stream of sample water along the first fluid return path.”). Edson teaches that sampling methods include analyzing the microplastic particles that are collected, and calculating the plastic concentration based on the volume of water that was sieved through the net during the sample time (see [0003]).
Edson is silent towards the use of microslit filters and performing a first analytical assay comprising electron microscopy, electron dispersive spectroscopy, electron energy loss spectroscopy, Fourier-transformed infrared spectroscopy, Raman spectroscopy, or any combination thereof.
Rahman teaches a method (see abstract, “a method for separating a biological entity from a sample volume is also provided”) comprising:
contacting a liquid sample suspected of having one or more microparticle(s) with a microslit filter (see [0239]-[0241] Figs. 11A-11B apparatus and method for circulating tumor cells (CTCs) isolation from whole blood…white blood cells (WBCs) within the sample were depleted by immunomagnetic separation before being flowed down to the chip 900 to retain CTCs, see [0223] “A micro slit membrane was designed to deplete platelets, RBCs, smaller-sized WBCs, such as lymphocytes, monocytes, and granulocytes that escaped immunomagnetic depletion, while retaining the majority of the other nucleated cells”, see [0242] “The microfiltration process of 4-ml blood assay was completed in less than 5 minutes. Approximately 2 mL of 1. PBS was introduced and flowed continuously to wash and remove the remaining RBCs on the micro slit membrane 800 in the microfluidic chamber 904.”) comprising
a plurality of openings, wherein the openings are cubic prisms, rectangular prisms, or trapezoids (see fig. 8, fig, 18c, [0223] “Compared to commonly used circular/hexagonal microfilters openings, the rectangular slit design has the advantage of defraying the pressure applied across the cells trapped on the membrane and preserving the viability and morphology of target cells.”) have a width from 0.5µm to 15µm and a length from 5µm to 100µm ([0223] “The membrane includes periodically arranged precise slits with a slit dimension of approximately 5.5-µm in width and 40- µm in length.”) and
have an aspect ratio from 1:0.33 to 1:200 (instant applications specification
teaches that the aspect ratio is in terms of width to length, and that the aspect ratio would be
determined by dividing the length by the width [0108]. The aspect ratio for Rahman is (40/5.5)=
1:7.27) and
the microslit filter has a thickness from 50 nm to 25µm, a porosity from 1% to 75%
(see [0285] “The membrane 1800 has an active diameter of about 21 mm, as represented within the dotted circle 1802, and a thickness of about 10µm, and containing slits, as represented by 1804 for some slits, with slit dimension approximately 5.5x40 µm, and a fill factor of approximately 39%.”), and
optionally washing the one or more retained particle(s) (see [0242] The microfiltration
process of 4-ml blood assay was completed in less than 5 minutes. Approximately 2 mL of 1.
PBS was introduced and flowed continuously to wash and remove the remaining RBCs on the
micro slit membrane 800 in the microfluidic chamber 904. Fixation of cells followed by the
staining protocol was initiated after the washing step.”), and
subsequentially measuring the quantity of the one or more retained microparticles directly on the microslit filter to determine the concentration of the one or more microparticles present in the liquid sample (see [0256] “Next, various concentrations of cell lines were spiked in 2-mL of whole blood and processed through the cell isolation system 1140 (FIG. 11B). The isolated cancer cells and other nucleated cells were retained on the micro slit membrane 800 after the microfiltration process. The isolated target cells were fixed and stained according to the above-described staining protocol for CTC identification and counting”, see [0244] “Cell counting and image capturing were performed using a 40x objective lens.”),
wherein measuring the quantity of the one or more retained microplastic particle(s) comprises optical imaging, electronic interrogation, optical diffraction, transmembrane pressure, or a combination thereof (see [0256] “The isolated target cells were fixed and stained according to the above-described staining protocol for CTC identification and counting.”, see [0244] “Cell counting and image capturing were performed using a 40x objective lens.”).
Rahman teaches performing a first analytical assay comprising an electron microscopy (see [0030], see fig. 5).
It would have been prima facia obvious, at the time of the instant application, to use the plastic microparticles of Edson with the methods of filtering microparticles with a microslit filter taught by Rahman. Rahman demonstrates the usefulness of using microslit filters for microparticles such as the microplastic particles taught by Edson.
Regarding claim 82, Edson teaches a method for sampling microplastics (see [0005] “In particular embodiments, methods and systems are provided which pertain to the automation of microplastic particle sampling, with the potential to provide autonomous sampling for days, weeks or even months at sea without the need for human intervention and costly time on research vessels.”).
Edson teaches contacting a liquid sample with a filter and using filters to collect the microplastics (see [0006] “In certain aspects, the present disclosure pertains to automated systems for sampling particles in a water sample from a body of water over a sampling period. These systems may comprise: (a) a power supply; (b) a fluid intake path configured to receive a stream of sample water from the body of water as a result of an action of one or more pumps; (c) a detection system configured to detect particles in the stream of sample water; (d) a first fluid return path that is configured to receive and return the sample water to the body of water; (e) a second fluid return path comprising a first particle filter that is configured to receive the stream of sample water, pass the stream of sample water through the first particle filter, and return the sample water to the body of water; (f) a controller that is configured to (i) direct the stream of sample water along the first fluid return path until one or more particles are detected, (ii) in the event of detection of one or more particles by the detection system, direct the stream of sample water along the second fluid return path for a predetermined period, (ii) after the predetermined period, redirect the stream of sample water along the first fluid return path.”). Edson teaches that sampling methods include analyzing the microplastic particles that are collected, and calculating the plastic concentration based on the volume of water that was sieved through the net during the sample time (see [0003]).
Edson is silent towards the use of microslit filters, the use of silicon nitride and a metal coating, and performing a first analytical assay comprising electron microscopy, electron dispersive spectroscopy, electron energy loss spectroscopy, Fourier-transformed infrared spectroscopy, Raman spectroscopy, or any combination thereof, measuring the quality of the retained microparticles as a single or replicate instances, preparing upstream samples, and the use of analytical assays.
Rahman teaches a method (see abstract, “a method for separating a biological entity from a sample volume is also provided”) comprising:
contacting a liquid sample suspected of having one or more microparticle(s) with a microslit filter (see [0239]-[0241] Figs. 11A-11B apparatus and method for circulating tumor cells (CTCs) isolation from whole blood…white blood cells (WBCs) within the sample were depleted by immunomagnetic separation before being flowed down to the chip 900 to retain CTCs, see [0223] “A micro slit membrane was designed to deplete platelets, RBCs, smaller-sized WBCs, such as lymphocytes, monocytes, and granulocytes that escaped immunomagnetic depletion, while retaining the majority of the other nucleated cells”, see [0242] “The microfiltration process of 4-ml blood assay was completed in less than 5 minutes. Approximately 2 mL of 1. PBS was introduced and flowed continuously to wash and remove the remaining RBCs on the micro slit membrane 800 in the microfluidic chamber 904.”) comprising
a plurality of openings, wherein the openings are cubic prisms, rectangular prisms, or trapezoids (see fig. 8, fig, 18c, [0223] “Compared to commonly used circular/hexagonal microfilters openings, the rectangular slit design has the advantage of defraying the pressure applied across the cells trapped on the membrane and preserving the viability and morphology of target cells.”) have a width from 0.5µm to 15µm and a length from 5µm to 100µm ([0223] “The membrane includes periodically arranged precise slits with a slit dimension of approximately 5.5-µm in width and 40- µm in length.”) and
have an aspect ratio from 1:0.33 to 1:200 (instant applications specification
teaches that the aspect ratio is in terms of width to length, and that the aspect ratio would be
determined by dividing the length by the width [0108]. The aspect ratio for Rahman is (40/5.5)=
1:7.27) and
the microslit filter has a thickness from 50 nm to 25µm, a porosity from 1% to 75%
(see [0285] “The membrane 1800 has an active diameter of about 21 mm, as represented within the dotted circle 1802, and a thickness of about 10µm, and containing slits, as represented by 1804 for some slits, with slit dimension approximately 5.5x40 µm, and a fill factor of approximately 39%.”), and
optionally washing the one or more retained particle(s) (see [0242] The microfiltration
process of 4-ml blood assay was completed in less than 5 minutes. Approximately 2 mL of 1.
PBS was introduced and flowed continuously to wash and remove the remaining RBCs on the
micro slit membrane 800 in the microfluidic chamber 904. Fixation of cells followed by the
staining protocol was initiated after the washing step.”), and
subsequentially measuring the quantity of the one or more retained microparticles directly on the microslit filter to determine the concentration of the one or more microparticles present in the liquid sample (see [0256] “Next, various concentrations of cell lines were spiked in 2-mL of whole blood and processed through the cell isolation system 1140 (FIG. 11B). The isolated cancer cells and other nucleated cells were retained on the micro slit membrane 800 after the microfiltration process. The isolated target cells were fixed and stained according to the above-described staining protocol for CTC identification and counting”, see [0244] “Cell counting and image capturing were performed using a 40x objective lens.”),
wherein measuring the quantity of the one or more retained microplastic particle(s) comprises optical imaging, electronic interrogation, optical diffraction, transmembrane pressure, or a combination thereof (see [0256] “The isolated target cells were fixed and stained according to the above-described staining protocol for CTC identification and counting.”, see [0244] “Cell counting and image capturing were performed using a 40x objective lens.”).
Rahman teaches where the microslit filters comprise silicon nitride and metal coating (see [0205] and [0206]).
It would have been prima facia obvious, at the time of the instant application, to use the plastic microparticles of Edson with the methods of filtering microparticles with a microslit filter taught by Rahman. Rahman demonstrates the usefulness of using microslit filters for microparticles such as the microplastic particles taught by Edson.
Regarding claim 7, Rahman teaches wherein the measuring the quantity of retained
microparticles of interest is performed as a single instance or as replicate instances (see [0256] “The isolated cancer cells and other nucleated cells were retained on the micro slit membrane 800 after the microfiltration process. The isolated target cells were fixed and stained according to the above-described staining protocol for CTC identification and counting.”, see [0266] “These samples were processed through the CTC isolation and enumeration system 1140. The system 1140 successfully detected CTCs… as shown in table 1, see [0138] “The surface treatment protocol may facilitate binding between a substrate (e.g. a plastic substrate) and antibody, hence capturing (or trapping) blood cells through antibody antigen specific binding between proteins on blood cells.”).
Regarding claim 10, Rahman teaches preparing one or more upstream sample (see [0240] “The setup 1100 includes a functionalized syringe barrel, e.g. a 5-ml syringe barrel 1102
containing blood sample conjugated with TAC and magnetic particle complex, placed within a
magnet 1104 for immunomagnetic WBC depletion.”, see [0250]-[0251] “Upstream Immunomagnetic WBC Depletion. A simple yet effective upstream immunomagnetic WBC depletion method, directly in whole blood, has been developed. The results of WBC depletion efficiency using the modified protocol of various embodiments are shown in FIG. 12.”).
Regarding claim 11, Rahman teaches comprising performing one or more first analytical assay on the one or more retained microplastic particle (see [0262] “The final assay purity was determined by counting the number of nucleated cells retained on the micro slit membrane alongside cancer cells.”).
It would have been obvious to one of ordinary skill in the art at the time the application
was filed to consider combining the methods of Rahman with the methods of Edson as they
both teach filtration of particles. Given the high level of skill in the art as evidenced by Rahman
and Edson, one of ordinary skill in the art would have considered combining Rahman’s microparticle microslit filtration methods with Edson’s methods of filtering microplastic particles.
Edson provides motivation by teaching that providing an automated method of treating and
testing for the presence of microplastic particles in a liquid sample without any need for human
intervention and costly time (see [0005]). Edson teaches that microplastic particles are pieces of plastic that are 5mm or smaller in diameter (see [0001]). Edson also teaches that the plastic
particles may range from 0.5 mm to 8 mm in diameter, but they are more typically found to be
0.5mm to 4 mm in diameter (see [0030]). Rahman teaches the microslit filter having width of 0.5µm to 15µm (see [0223]). While Rahman is drawn towards a different target (blood), the instant applications measurements (a width from 0.5µm to 100µm and have an aspect ratio from 1:30 to 1:200, and the microslit filter having a thickness from 50nm to 25µm, and a porosity from 1%-75%) are all elements taught by Rahman’s microslit filters. One of ordinary skill in the art would have reasonable expectation of success to combine the microplastic particles of Edson with the microslit filters of Rahman, because the microslit filters taught by Rahman because Rahman teaches that the advantage of defraying the pressure applied across the cells trapped on the membrane and preserving the viability of the molecule (see [0223]). Rahman, like the instant application, use the microslit for the same reasons, such as, a filter to separate or retain the particle (see abstract, see [0073]). One of ordinary skill in the art would have considered using the microslit filters taught by Rahman with the microplastic particles taught by Edson, because the microslit filter sizing it one that works with microplastic particles (see the instant applications sizing of claim 1 and Rahman’s teachings of the sizing of the microslit filter). Rahman demonstrates the usefulness of using microslit filters for microparticles such as the microplastic particles taught by Edson It would have been obvious to one of ordinary skill in the art to use the microslit filters as taught by Rahman with the microplastic particles taught by Edson because the microslit filters has the right sized opening’s to capture the microplastic particles and it has been proven to be an efficient filter system for complex samples and the advantages of defraying the pressure across the particles on the membrane and preserving viability of the particles. The artisan would have had reasonable expectation of success based on the cumulative disclosures of these prior art references.
Claims 21-23, 25, 28, and 78 are rejected under 35 U.S.C. 103 as being unpatentable
over Edson and Rahman, as applied to claims 1, 6-8, 10-11, and 80 above, and in further view
of Chiu et al., (US 2016/0146823 A1; published on 05/26/2016; effectively filed on 07/01/2014)
(IDS filed on 05/24/2021).
The teachings of Edson and Rahman as they pertain to claims 1, 6-8, 10-11, and 80 are
discussed in the 35 U.S.C. 103 rejection above.
Regarding claim 25, Rahman teaches preparing one or more upstream sample (see [0240] “The setup 1100 includes a functionalized syringe barrel, e.g. a 5-ml syringe barrel 1102
containing blood sample conjugated with TAC and magnetic particle complex, placed within a
magnet 1104 for immunomagnetic WBC depletion.”, see [0250]-[0251] “Upstream Immunomagnetic WBC Depletion. A simple yet effective upstream immunomagnetic WBC depletion method, directly in whole blood, has been developed. The results of WBC depletion efficiency using the modified protocol of various embodiments are shown in FIG. 12.”).
Rahman is silent towards wherein the contacting a liquid sample with two or more microslit filters comprises fluidic contact of the liquid sample with two or more first filtration membranes, two or more fluidic cavities, and two or more second filtration membranes, wherein the contacting a liquid sample with two or more microslit filters comprises fluidic contact of the liquid sample with two or more first filtration membranes, two or more fluidic cavities, and two or more second filtration membranes, the contacting a liquid sample comprising a plurality of one or more microplastic particle with two or more microslit filters, includes gravity flow, hydrostatic pressure, pumping, vacuum, centrifugation, gas pressurization, or tangential flow, the contacting comprises successively contacting the liquid sample with two or more microslit filters, such that two or more populations of microplastic particle(s) are successively retained by the two or more microslit filters.
Regarding claim 78, Chiu teaches wherein the contacting comprises successively
contacting the liquid sample with two or more microslit filters, such that two or more populations
of microplastic particle(s) are successively retained by the two or more microslit filters (see [0068] “the method can be combined with a microfluidic device. The microfluidic device can be used to isolate analytes from a sample.”, see [0051] “the analytes are further purified on the microfluidic chip, such as by passing the fluid through a filter or an array of microslits. The analytes can be collected at the filter or on the array of microslits.”, see [0088] “In some aspects, the eDAR platform can include an apparatus for the capture of more than one analyte (e.g., rare cell). The “dual-capture' eDAR can separate multiple rare cells from a mixed sample. The mixed sample (e.g., fluid sample) can be labeled with a detection reagent and entered into the top of the "dual- capture' apparatus at a main channel… Two subpopulations of rare cells can be separated and trapped on two different filtration areas on the same microfluidic chip.”, see [0124] “Microslits can be used as a source of filtration.”).
Regarding claim 21, Chiu teaches wherein the contacting a liquid sample with two or
more microslit filters, comprises fluidic contact of the liquid sample with two or more first filtration membranes (see [0088] “In some aspects, the eDAR platform can include an apparatus for the
capture of more than one analyte (e.g., rare cell). The “dual-capture' eDAR can separate
multiple rare cells from a mixed sample. The mixed sample (e.g., fluid sample) can be labeled
with a detection reagent and entered into the top of the "dual-capture' apparatus at a main
channel… Two subpopulations of rare cells can be separated and trapped on two different
filtration areas on the same microfluidic chip.”, see [0171] “In some aspects, the filtration area of the dual-capture eDAR can be built using microslits (described before). Two subpopulations of
CTCs can be separated and trapped on two different filtration areas on the same microfluidic
chip.”),
two or more fluidic cavities (see [0171] “The dual-capture eDAR apparatus can use a fluidic switching scheme (FIG. 11). The labeled sample can be introduced into the main channel on the top. Buffer can flow in the two side channels to control the hydrodynamic Switching of the blood flow using two Solenoids. In some aspects, the filtration area of the dual-capture eDAR can be built using microslits (described before). Two subpopulations of CTCs can be separated and trapped on two different filtration areas on the same microfluidic chip.”), and
two or more second filtration membranes (see [0088] “Two subpopulations of rare cells can be separated and trapped on two different filtration areas on the same microfluidic chip.”, see [0171] as shown in fig.11, the dual capture apparatus used includes a second filtration area…” the filtration area of the dual-capture eDAR can be built using microslits”, i.e. more than one).
Regarding claim 22, Chiu teaches wherein the measuring the quantity of the two or more populations of retained particles of interest is performed as a single instance or as replicate instances for each particle population (see [0047] “In some aspects, an el DAR apparatus can be used to (i) detect the presence or absence of a rare particle (e.g., rare cell) in an aliquot of the fluid sample, (ii) rank the aliquot according to the presence or absence of a rare particle”, see [0065] “As used herein, the term “ranking' refers to assessing a quantitative property, qualitative property, or importance of an aliquot by categorization.”, see [0168] “In some aspects, a digital processor accepts a signal from the detection device and through an algorithm to rank the aliquot. The digital processor can direct the aliquot into the appropriate channel based on the value of the ranking (e.g., the presence, absence, quantity, identity, or composition of rare particles in the fluid sample). eDAR can consist of one, two, three, four, five or six detection devices and one, two, three, four, five or six interrogation devices, or multitudes of detection devices and interrogation devices.”).
Regarding claim 23, Chiu teaches wherein the contacting a liquid sample comprising a
plurality of one or more target particles with two or more microslit filters, includes gravity flow,
hydrostatic pressure, pumping, vacuum, centrifugation, gas pressurization, or tangential flow
(see [0087] “The eDAR apparatus can include a microscope equipped with sources of radiation
(e.g., lasers) for excitation and a mode of detection, sources of light (e.g., photobleaching), a
timer, tubing, a waste-collection device, a camera for imaging tagged analytes (e.g., cells),
pumps to control the flow of fluid in and out of the microfluidic chip”, see [0148] “In some aspects, the flow can be delivered by, for example, methods and devices that induce hydrodynamic fluidic pressure, which includes but is not limited to those that operate on the basis of mechanical principles (e.g., external syringe pumps, pneumatic membrane pumps, vibrating membrane pumps, vacuum devices, centrifugal forces, and capillary action)”).
Regarding claim 28, Chiu teaches performing one or more first analytical assay on the
two or more populations of retained target particles (see [0068] “the method can be combined with a microfluidic device. The microfluidic device can be used to isolate analytes from a sample.”, see [0051] “the analytes are further purified on the microfluidic chip, such as by passing the fluid through a filter or an array of microslits. The analytes can be collected at the filter or on the array of microslits.”, see [0088] “In some aspects, the eDAR platform can include an apparatus for the capture of more than one analyte (e.g., rare cell). The “dual-capture' eDAR can separate multiple rare cells from a mixed sample. The mixed sample (e.g., fluid sample) can be labeled with a detection reagent and entered into the top of the "dual-capture' apparatus at a main channel… Two subpopulations of rare cells can be separated and trapped on two different filtration areas on the same microfluidic chip.”, see [0124] “Microslits can be used as a source of
filtration.”).
It would have been obvious to one of ordinary skill in the art at the time the application
was filed to combine the methods of Edson and Rahman with the methods of Chiu. Given the
high level of skill in the art as evidenced by Edson, Rahman and Chiu, one of ordinary skill in
the art would have considered combining Edson and Rahman’s methods of using microslit filters
to capture microplastic particles with Chiu’s teachings of personalized microfiltration. Chiu
provides motivation for using eDAR as a microfluidic device, as it can be used to rapidly analyze
a fluid containing a mixed population of analytes with a high recovery rate and a low false
positive rate (see [0074]). The artisan would have had reasonable expectation of success based on the cumulative disclosures of these prior art references.
Claim 77 is rejected under 35 U.S.C. 103 as being unpatentable over Edson, Rahman
and Chiu as applied to claims 21-23, 25, 28, and 78 above, and in further view of Roussie et al.,
(WO 2019/036545 A1; published on 02/21/2019; effectively filed on 08/16/2017) (IDS filed on
05/24/2021).
The teachings of Edson, Rahman and Chui as they pertain to claims 21-23, 25, 28, and
78 are discussed in the 35 U.S.C. 103 rejection above. Edson, Rahman and Chiu are silent towards the transmembrane pressure dropping.
Regarding claim 77, Roussie teaches wherein the measuring by transmembrane
pressure comprises a transmembrane pressure drop (see [0097] “the fluidic device uses
transmembrane pressure differential and tangential flow, where contact with the microslit filter
involves flow that is tangential to the microslit filter surface, the biofluid or the biofluid-complex
mixture is introduced to the cis-side of the filter, bulk flow is initiated on both cis- and trans-sides
of the filter such that a transmembrane pressure is generated (i.e., relative negative pressure on
the trans-filter side), thus initiating flux from the cis- to the trans-side of the filter.”).
It would have been obvious to one of ordinary skill in the art at the time of the application
to combine the teachings of Edson, Rahman, Chiu, and Roussie as they all teach methods of
isolation and detection of a microplastic particles using microslit filters. Given the high level of
skill in the art as evidenced by Edson, Rahman, Chiu, and Roussie, one of ordinary skill in the
art would have considered combining Edson, Rahman and Chiu’s teachings of microfiltration
with Roussie’s teachings of efficient isolation and the use of transmembrane pressure to
measure the quantity of retained particles of interest. Roussie teaches that negative
transmembrane pressure on the trans-filter side initiates flux from the cis- to the trans- side of
the filter, particles to pass or travel through the filter (see [0097]). The artisan would have had
reasonable expectation of success based on the cumulative disclosures of these prior art
references.
Claim 79 is rejected under 35 U.S.C. 103 as being unpatentable over Edson and
Rahman, as applied to claims 1, 6-8, 10-11, and 80 above, and in further view of Claro et al.,
“Characterization of Microplastics by Raman Spectroscopy” (2017).
The teachings of Edson and Rahman as they pertain to claims 1, 6-8, 10-11, and 80 are
discussed in the 35 U.S.C. 103 rejection above. Edson and Rahman are silent towards the
optical imaging comprising of infrared spectroscopy or Raman spectroscopy.
Claro teaches the characterization of microplastics by Raman spectroscopy (see page 120 “In the following sections, an overview of the application of Raman spectroscopy in the
characterization of microplastics is introduced, opening with a brief description of the principles
of Raman spectroscopy and some of its experimental apparatus in Section 2.”).
Regarding claim 79, Claro teaches wherein the optical imaging comprises infrared
spectroscopy or Raman spectroscopy (see page 120 “In the following sections, an overview of the application of Raman spectroscopy in the characterization of microplastics is introduced, opening with a brief description of the principles of Raman spectroscopy and some of its
experimental apparatus in Section 2.”).
It would have been obvious to one of ordinary skill in the art at the time of the instant
application to consider combining the methods of Rahman and Edson with the methods of Claro
as they teach detection of microplastic particles. Given the high level of skill in the art as
evidenced by Rahman, Edson, and Claro one of ordinary skill in the art would have considered
combining Rahman’s microparticle microslit filtration methods with Edson’s methods of filtering
microplastic particles with Claro’s methods of using Raman spectroscopy for characterization of
microplastics. Claro provides motivation by teaching that Raman spectroscopy has proven to be
a powerful tool for identification of microplastic pollutants (see page 127, see page 147). The artisan would have had reasonable expectation of success based on the cumulative disclosures of these prior art references.
Claim Rejections - 35 USC § 103-Response to Arguments
The arguments filed on 07/31/2025 have been considered by the examiner.
On pp. 8-9 Applicant argues that if the measurement of cells on the microslit filter is substituted into the method of Edson, the principal operation of Edson would change.
However, the applicant did not explicitly point out that the combined references of Edson and Rahman would render the invention inoperable. Edson does teach a system that samples microplastics, one of ordinary skill in the art would have considered using the methods of Edson for sampling microplastics with measurement of the cells that are on the filter, as Edson teaches that the microplastic particles that are collected undergo further analyzing, which could include measuring the microplastics. Further, Edson teaches that particles flowing through the system can be detected and grouped into a relative size category (see [0036]), thus looking at their measurements and grouping them in categories based on those measurements.
On p. 9 applicant argues that Edson clearly teaches filtration of the waste stream after detection of the microparticles. However, Rahman teaches contacting a liquid sample with a microslit filter (see [0223] and [0242]), and then subsequently measuring the quantity of the one or more retained microparticles (see [0256] and [0244]). Rahmen explicitly states that the sample contacts the microslit filter, then the cells that were isolated on the microslit filter were then measured (see [0256]). Thus, Rahmen teaches measuring the microparticles after they were in contact with the microslit filter. Edson teaches the microparticles being microplastic particles.
On pp. 9-10 applicant argues that the citation of Edison teaching that sampling methods include analyzing the microplastic particles that are collected, and calculating the plastic concentration based on the volume of water that was sieved through the net during the sample time (see [0003]) is inappropriate as it is from the background and refers to current or past marine microplastics sampling methods. However, regardless of the teaching being in the background and mentioning current or past methods of measuring microparticles, the reference teaches methods of filtering microplastic particles.
On p. 10 applicant that Edson does not teach measuring the quantity of the one or more retained microplastic particle(s) directly on the microslit filter to determine the concentration of microplastic particle(s) present in the liquid sample recited in claim 1. However, Rahman teaches measuring the quantity of the one or more retained microplastic particle(s) directly on the microslit filter to determine the concentration of microplastic particle(s) present in the liquid sample (see [0256] and [0244]).
On p.10 applicant argues that neither the methods nor the systems disclosed in Edson describe measuring or analyzing microplastic particles. However, Edson teaches that if a particle is detected in a sample, the microcontroller uses a sizing algorithm that is based on the signal drop of the photodetectors and the particle breaks the lasers path (looking at the size/measurement of the particle) (see [0037]). Further, Edson teaches that the particle on the filter column is then captured, then the system can begin sample processing (see [0037]). Therefore, Edson does teach measuring/analyzing microplastic particles.
On pp. 10-11 applicant argues there is no motivation for one of ordinary skill in the art to combine the references Edson and Rahman. Applicant further argues that in a prima facia case of obviousness, it requires a clearly articulated motivation to carry out the posited combination of Rahman.
In response to applicant’s argument that there is no teaching, suggestion, or motivation
to combine the references, the examiner recognizes that obviousness may be established by
combining or modifying the teachings of the prior art to produce the claimed invention where
there is some teaching, suggestion, or motivation to do so found either in the references
themselves or in the knowledge generally available to one of ordinary skill in the art. See In re
Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d
1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d
1385 (2007).
In this case, one of ordinary skill in the art would have considered using the
microslit filters taught by Rahmen with the microplastic particles taught by Edson because the
microslit filters have the right sized openings to capture the microplastic particles and it has
been proven to be an efficient filter system for complex samples.
On p. 11 applicant argues that it is not obvious to combine Edson and Rahman because Rahman teaches the right sized openings for the microparticles and the microslit filters have been proven to be an efficient filter system for complex samples is insufficient to establish that one of ordinary skill in the art would have been motivated to combine Edson and Rahman. However, one of ordinary skill in the art would have been motivated to comb