DETAILED ACTION
Response to Amendment
This is a final office action in response to a communication filed on xxx, 2025. Claims 1-38 are pending in the application.
Status of Objections and Rejections
All objections and rejections under 35 U.S.C. §112 from the previous office action are withdrawn in view of Applicant’s amendment.
All rejections under 35 U.S.C. §103 are maintained.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim(s) 1, 7-16, 27-29, 31, 35-38 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sanders (US 2022/0288588) in view of Dimov (I.K. Dimov, Stand-alone self-powered integrated microfluidic blood analysis system (SIMBAS), Lab on a Chip, 2011, vol. 11, pp. 845-50).
Regarding claim 1, Sanders teaches a microfluidic passive sample separation device (Fig. 2: microfluidic passive plasma separation device 200) comprising:
a body (Fig. 2; ¶90: the body of device 200) defining an inlet (Fig. 2; ¶88: aperture 212) and an outlet (Fig. 2; ¶88: aperture 214), the body housing
a filter (Fig. 2; ¶92: an engineered filter pad 260) for filtering a liquid sample in contact therewith and for producing a filtrate (¶92: designed to retain the red and white blood cells and the platelets present in whole blood and allow only the plasma and its dissolved constituents to pass through); and
a plurality of capillaries (Fig. 2; ¶101: a plurality of plasma collection channels 273) configured to withdraw the filtrate from the filter by capillary force (¶36: to a plasma collection reservoir by capillary force), each capillary having
a first end fluidly connected to the filter for receiving the filtrate (Fig. 2: indicating the plurality of capillary channels of 273 each having an end receiving the filtration passing through the filter pad 260); and
a second end (Fig. 2: indicating the second ends of capillary channels 273 converging into the capillary 275).
Sanders further discloses the microfluidic capillary channel acts as a capillary pump, creating a lower pressure at the outlet of the engineered filter pad that accelerates the blood separation therethrough (¶9), which provide a sufficient pressure to overcome the capillary forces (¶38). Sanders does not explicitly disclose a capillary micropump fluidly connected to the second end of capillaries for dispensing the filtrate to the capillary pump; the capillary micropump being configured to receive the filtrate and to pump the filtrate to the outlet.
However, Dimov teaches a two-step, self-contained and self-powered
integrated microfluidic blood analysis system (SIMBAS) that integrates whole-blood plasma separation from red and white blood cells with multiple immunoassays (Fig. 1; p.846, col. 1, para. 3). The device includes suction chambers for fluid propulsion (Fig. 1), which regulates the total volume of plasma and stops the flow before the trench filters are overfilled (Fig. 1). Thus, the suction chambers are deemed to be a capillary micropump fluidly connected to the channels of plasma extraction and for dispensing the plasma.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Sanders by incorporating the suction chambers between the plurality of plasma collection channels and the outlet for generating a flow due to pressure difference as taught by Dimov because the suction chambers would be able to propels fluid and regulate the plasma volume and stop the flow before overfilled (Fig. 1) so that the device does not require any external support equipment with low-cost, high-volume manufacturing (p.846, col. 1, para. 3). Here, the claimed limitations are obvious because all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results. MPEP 2143(I)(A). The combined Sanders and Dimov would necessarily result in the capillary micropump between the end of capillaries and the outlet, and thus dispensing the filtrate from the end of capillaries to the micropump and then receiving and pumping the filtrate to the outlet.
Regarding claim 7, Sanders teaches wherein the filter is a filter membrane (¶93: separation membrane).
Regarding claim 8, Sanders teaches wherein the filter membrane has a pore size of about 0.3 µm to about 10 µm (¶94: 8 µm).
Regarding claim 9, the designation “wherein the microfluidic passive filtration device is inverted or non-inverted” is deemed to be functional limitation in apparatus claims. MPEP 2114 (II). "[A]pparatus claims cover what a device is, not what a device does." Hewlett-Packard Co. v. Bausch & Lomb Inc., 909 F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990) (emphasis in original). A claim containing a "recitation with respect to the manner in which a claimed apparatus is intended to be employed does not differentiate the claimed apparatus from a prior art apparatus" if the prior art apparatus teaches all the structural limitations of the claim. Ex parte Masham, 2 USPQ2d 1647 (Bd. Pat. App. & Inter. 1987). Here, Sanders in view of Dimov teaches all structural limitations of the presently claimed microfluidic passive sample separation device and thus it is capable of being used inverted or non-inverted.
Regarding claim 10, Sanders and Dimov disclose all limitations of claim 1 as applied claim 1, but fail to teach wherein the inlet defines a volume of between 50 µl to about 200 µl.
However, Sanders teaches an initial whole blood sample having a volume of from about 100 µl to about 150 µl (¶127), which overlaps the claimed range.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Sanders and Dimov by adjusting the inlet volume within the claimed ranges because it is suitable inlet volume in plasma separation device. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05(I).
Regarding claim 11, Sanders teaches wherein the liquid sample comprise whole blood (¶2: separating plasma from whole blood).
Regarding claim 12, Sanders teaches wherein the filtrate comprises an analyte (¶139: the separated plasma flows directly into a diagnostic device where it can be analyzed).
The limitation “the analyte optionally comprises a nucleic acid, DNA, circulating DNA, high- risk HPV circulating DNA, high-risk HPV16 circulating DNA, a protein, an antibody, an antigen, a metabolite; a toxin; a biotoxin, such as domoic acid or okadaic acid; a small molecule; a cell; a bacterium; a virus; or an inflammatory marker, such as interleukins, cytokines, creative protein, pro-calcitonin, or pre-sepsin” is optional and not required in the prior art.
Regarding claim 13, Sanders teaches wherein the filtrate comprises plasma (¶2: separating plasma from whole blood).
Regarding claim 14, Sanders teaches wherein the microfluidic passive plasma separation device is suitable for point-of-care use (¶17: integrated directly to a POC microfluidic diagnostic device).
Regarding claim 15, Sanders teaches the device further comprising a capillary microchannel (Fig. 2; ¶101: first microfluidic capillary channel 275/277) and a capillary microwell housed in the body (Fig. 2: aperture 212 forming a microwell in the first layer 210),
the microchannel having a first end fluidly connected to the inlet for receiving the liquid sample (Fig. 2: the capillary channel 275 is fluidly connected to the aperture 212 for receiving the liquid sample), and a second end fluidly connected to the microwell for dispensing the liquid sample to the microwell (Fig. 2: the capillary channel 277 is fluidly connected to the microwell at the inlet), the microchannel configured to move the liquid sample from the inlet to the microwell by capillary force (¶36: to a plasma collection reservoir by capillary forces), and
the microwell having a first end fluidly connected to the microchannel for receiving the liquid sample (Fig. 2: indicating the top of the microwell is for receiving the sample and fluidly connected to capillary channels 275/277), and a second end coupled to the filter (Fig. 2: indicating the bottom of the microwell coupled to the filter pad 260).
The designation “the microwell configured to move the liquid sample from the microchannel to the filter by capillary force” is deemed to be functional limitation in apparatus claims. MPEP 2114 (II). "[A]pparatus claims cover what a device is, not what a device does." Hewlett-Packard Co. v. Bausch & Lomb Inc., 909 F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990) (emphasis in original). A claim containing a "recitation with respect to the manner in which a claimed apparatus is intended to be employed does not differentiate the claimed apparatus from a prior art apparatus" if the prior art apparatus teaches all the structural limitations of the claim. Ex parte Masham, 2 USPQ2d 1647 (Bd. Pat. App. & Inter. 1987). Here, Sanders in view of Dimov teaches all structural limitations of the presently claimed microfluidic passive sample separation device, including a microwell, and thus the microwell is capable of moving the liquid sample from the microchannel to the filter by capillary force.
Regarding claim 16, Sanders teaches the device further comprising a sensor for detecting an analyte (¶17: integrated directly to a point of care (POC) microfluidic diagnostic device), the sensor being fluidly connected to the outlet (¶139: the separated plasma flows directly into a POC diagnostic device where it can be analyzed).
The designation “the sensor optionally comprising an electrochemical sensor, an optical sensor, a piezoelectric sensor, or a photodetector” is optional and not required in the prior art.
Regarding claim 27, Sanders teaches a microfluidic passive sample separation device (Fig. 2: microfluidic passive plasma separation device 200) comprising
a body (Fig. 2; ¶90: the body of device 200) defining an inlet (Fig. 2; ¶88: aperture 212) and an outlet (Fig. 2; ¶88: aperture 214), the inlet defining a volume and configured to accept a liquid sample (Fig. 2: indicating the inlet receiving a volume of the liquid sample),
the body housing:
a capillary microchannel (Fig. 2; ¶101: first microfluidic capillary channel 275/277), a capillary microwell housed in the body (Fig. 2: aperture 212 forming a microwell in the first layer 210), and a filter (Fig. 2; ¶92: an engineered filter pad 260),
the microchannel having a first end fluidly connected to the inlet for receiving the liquid sample (Fig. 2: the capillary channel 275 is fluidly connected to the aperture 212 for receiving the liquid sample), and a second end fluidly connected to the microwell for dispensing the liquid sample to the microwell (Fig. 2: the capillary channel 277 is fluidly connected to the microwell at the inlet), the microchannel configured to move the liquid sample from the inlet to the microwell by capillary force (¶36: to a plasma collection reservoir by capillary forces), and
the microwell having a first end fluidly connected to the microchannel for receiving the liquid sample (Fig. 2: indicating the top of the microwell is for receiving the sample and fluidly connected to capillary channels 275/277), and a second end coupled to the filter (Fig. 2: indicating the bottom of the microwell coupled to the filter pad 260),
the filter (Fig. 2; ¶92: an engineered filter pad 260) configured to filter the liquid sample received from the microwell to produce a filtrate (¶92: designed to retain the red and white blood cells and the platelets present in whole blood and allow only the plasma and its dissolved constituents to pass through); and
a plurality of capillaries (Fig. 2; ¶101: a plurality of plasma collection channels 273) configured to withdraw the filtrate from the filter by capillary force (¶36: to a plasma collection reservoir by capillary force),
the plurality of capillaries configured to withdraw the filtrate from the filter by capillary force (¶36: to a plasma collection reservoir by capillary forces), each capillary having a first end fluidly connected to the filter for receiving the filtrate (Fig. 2: indicating the plurality of capillary channels of 273 each having an end receiving the filtration passing through the filter pad 260); and a second end (Fig. 2: indicating the second ends of capillary channels 273 converging into the capillary 275).
Sanders further discloses the microfluidic capillary channel acts as a capillary pump, creating a lower pressure at the outlet of the engineered filter pad that accelerates the blood separation therethrough (¶9), which provide a sufficient pressure to overcome the capillary forces (¶38). Sanders does not explicitly disclose a capillary micropump that is fluidly connected to the second end of each capillary for dispensing the filtrate to the capillary pump; the capillary micropump being configured to receive the filtrate and to pump the filtrate to the outlet.
However, Dimov teaches a two-step, self-contained and self-powered
integrated microfluidic blood analysis system (SIMBAS) that integrates whole-blood plasma separation from red and white blood cells with multiple immunoassays (Fig. 1; p.846, col. 1, para. 3). The device includes suction chambers for fluid propulsion (Fig. 1), which regulates the total volume of plasma and stops the flow before the trench filters are overfilled (Fig. 1). Thus, the suction chambers are deemed to be a capillary micropump fluidly connected to the channels of plasma extraction and for dispensing the plasma.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Sanders by incorporating the suction chambers between the plurality of plasma collection channels and the outlet for generating a flow due to pressure difference as taught by Dimov because the suction chambers would be able to propels fluid and regulate the plasma volume and stop the flow before overfilled (Fig. 1) so that the device does not require any external support equipment with low-cost, high-volume manufacturing (p.846, col. 1, para. 3). Here, the claimed limitations are obvious because all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results. MPEP 2143(I)(A). The combined Sanders and Dimov would necessarily result in the capillary micropump between the end of capillaries and the outlet, and thus dispensing the filtrate from the end of capillaries to the micropump and then receiving and pumping the filtrate to the outlet.
The designation “the microwell configured to move the liquid sample from the microchannel to the filter by capillary force” is deemed to be functional limitation in apparatus claims. MPEP 2114 (II). "[A]pparatus claims cover what a device is, not what a device does." Hewlett-Packard Co. v. Bausch & Lomb Inc., 909 F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990) (emphasis in original). A claim containing a "recitation with respect to the manner in which a claimed apparatus is intended to be employed does not differentiate the claimed apparatus from a prior art apparatus" if the prior art apparatus teaches all the structural limitations of the claim. Ex parte Masham, 2 USPQ2d 1647 (Bd. Pat. App. & Inter. 1987). Here, Sanders in view of Dimov teaches all structural limitations of the presently claimed microfluidic passive sample separation device, including a microwell, and thus the microwell is capable of moving the liquid sample from the microchannel to the filter by capillary force.
Regarding claim 28, Sanders teaches wherein the filter is vertically displaced relative to the microchannel (Fig. 2).
Regarding claim 29, Sanders teaches wherein the outlet is parallel to the inlet (Fig. 2).
Regarding claim 31, Sanders teaches wherein the capillary microchannel has a width between about 100 µm to about 1mm (¶134: the width of the narrow portion 775 may be about 0.5mm (=500 µm) whereas the width of the wide portion 777 may be about 1 mm).
Regarding claim 35, the designation “wherein the microfluidic passive filtration device is non-inverted” is deemed to be functional limitation in apparatus claims. MPEP 2114 (II). "[A]pparatus claims cover what a device is, not what a device does." Hewlett-Packard Co. v. Bausch & Lomb Inc., 909 F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990) (emphasis in original). A claim containing a "recitation with respect to the manner in which a claimed apparatus is intended to be employed does not differentiate the claimed apparatus from a prior art apparatus" if the prior art apparatus teaches all the structural limitations of the claim. Ex parte Masham, 2 USPQ2d 1647 (Bd. Pat. App. & Inter. 1987). Here, Sanders in view of Dimov teaches all structural limitations of the presently claimed microfluidic passive sample separation device and thus it is capable of being used non-inverted.
Regarding claim 36, the limitation “wherein the liquid sample comprises blood; whole blood; urine; seminal fluid; vaginal fluid; tissue; an aqueous solution; marine or freshwater water; a marine or freshwater plant; marine or freshwater food; phytoplankton; shellfish; food; or milk; or a combination thereof” is directed to a material or article worked upon. "Expressions relating the apparatus to contents thereof during an intended operation are of no significance in determining patentability of the apparatus claim." Ex parte Thibault, 164 USPQ 666, 667 (Bd. App. 1969). Furthermore, "[i]nclusion of material or article worked upon by a structure being claimed does not impart patentability to the claims." In re Young, 75 F.2d. 25 USPQ 69 (CCPA 1935) (as restated in In re Otto, 312 F.2d 937, 136 USPQ 458, 459 (CCPA 1963)). MPEP 2115.
Regarding claim 37, Sanders teaches wherein the filtrate comprises an analyte (¶139: the separated plasma flows directly into a diagnostic device where it can be analyzed).
The limitation “the analyte optionally comprises a nucleic acid, DNA, circulating DNA, high- risk HPV circulating DNA, high-risk HPV16 circulating DNA, a protein, an antibody, an antigen, a metabolite; a toxin; a biotoxin, such as domoic acid or okadaic acid; a small 55molecule; a cell; a bacterium; a virus; or an inflammatory marker, such as interleukins, cytokines, creative protein, pro-calcitonin, or pre-sepsin” is optional and not required in the prior art.
Regarding claim 38, Sanders teaches the device further comprising a sensor for detecting an analyte (¶17: integrated directly to a point of care (POC) microfluidic diagnostic device), the sensor being fluidly connected to the outlet (¶139: the separated plasma flows directly into a POC diagnostic device where it can be analyzed).
The designation “the sensor optionally comprising an electrochemical sensor, an optical sensor, a piezoelectric sensor, or a photodetector” is optional and not required in the prior art.
Claim(s) 2-3 and 32 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sanders in view of Dimov, and further in view of Yang (S. Yang, A microfluidic device for continuous, real time blood plasma separation, Lab on a Chip, 2006, vol. 6, pp. 871-880).
Regarding claim 2, Sanders and Dimov discloses all limitations of claim 1 as applied claim 1, but fails to teach wherein the plurality of capillaries are substantially parallel.
However, Yang teaches a microfluidic blood plasma separation device including a whole blood inlet, a purified plasma outlet, and five parallel plasma channels connected in between (Fig. 4). To obtain a larger plasma separation percent, additional plasma channels may be placed in parallel (p. 879, col. 2, para. 1) and also increase the total plasma separation volume (p. 880, col. 1, para. 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Sanders and Dimov by substituting the dendritic plasma channels with additional parallel plasma channels as taught by Yang because those additional parallel plasma channels would increase the total plasma separation volume and obtain a larger plasma separation percent (p. 880, col. 1, para. 2; p. 879, col. 2, para. 1). Here, the claimed limitations are obvious because all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results. MPEP 2143(I)(A).
Regarding claim 3, Sanders and Dimov disclose all limitations of claim 1 as applied claim 1, but fails to teach wherein each capillary has a width of about 8 µm to about 20 µm and is spaced about 8 µm to about 80µm pm from an adjacent capillary.
However, Yang teaches a microfluidic blood plasma separation device including a whole blood inlet, a purified plasma outlet, and five parallel plasma channels connected in between (Fig. 4). The width of all plasma channels is 9.6 µm (Fig. 4: caption) and are spaced from each other at a distance about 9.6 µm (Fig. 4: indicating the spacing is the same as the width of each channel).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Sanders and Dimov by adjusting the width and spacing of the plasma channels within the claimed ranges as suggested by Yang because those are suitable width and spacing for plasma channels in plasma separation device. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05(I). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985). MPEP 2144.05(I).
Regarding claim 32, Sanders and Dimov discloses all limitations of claim 27 as applied claim 27, but fails to teach wherein the plurality of capillaries are substantially parallel.
However, Yang teaches a microfluidic blood plasma separation device including a whole blood inlet, a purified plasma outlet, and five parallel plasma channels connected in between (Fig. 4). To obtain a larger plasma separation percent, additional plasma channels may be placed in parallel (p. 879, col. 2, para. 1) and also increase the total plasma separation volume (p. 880, col. 1, para. 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Sanders and Dimov by substituting the dendritic plasma channels with additional parallel plasma channels as taught by Yang because those additional parallel plasma channels would increase the total plasma separation volume and obtain a larger plasma separation percent (p. 880, col. 1, para. 2; p. 879, col. 2, para. 1). Here, the claimed limitations are obvious because all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results. MPEP 2143(I)(A).
The limitation “wherein optionally each capillary has a width of about 8 pm to about 20 pm and is spaced about 8 µm to about 80 µm from an adjacent capillary; or each capillary has a width of about 12 µm and is spaced about 40 µm from an adjacent capillary” is optional and not required in the prior art.
Claim(s) 4 and 33 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sanders in view of Dimov, and further in view of Juncker (US 2014/0332098).
Regarding claims 4 and 33, Sanders and Dimov disclose all limitations of claims 1 and 27 as applied claims 1 and 27, respectively, but fail to teach wherein the wherein the capillary micropump has at least a first end and a second end opposite the first end, and wherein the width of the micropump increases and then decreases between the first end and the second end.
However, Juncker teaches a “lab-on-a-chip” system and point-of-care (POC) device ([Abstract]), including a capillary pump (Fig. 2D). One example of the capillary pump (Fig. 5B; ¶97: capillary pump 540) having an inlet port (Fig. 5B; ¶97: inlet port 510) at one end and an outlet (Fig. 5B; ¶97: the vent 530) at the other opposite end (Fig. 5B), and the width of the capillary pump 540 increases and then decreases between the first end and the second end).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Sanders and Dimov by substituting the capillary pump (Dimov, Fig. 1: suction chamber) with the capillary pump as taught by Juncker because the capillary pump having its width increasing and then decreasing from one end to the other end is a suitable capillary pump for flow and the substitution would yield nothing more than predictable results. MPEP 2141(III)(B).
Claim(s) 5-6 and 34 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sanders in view of Dimov, and further in view of Madadi (H. Madadi, Self-driven filter-based blood plasma separator microfluidic chip for point-of-care testing, Biofabrication, 2015, vol. 7, 025007, pp. 1-11), and further in view of Ding (US 2014/0180201).
Regarding claims 5-6 and 34, Sanders and Dimov disclose all limitations of claims 1 and 27 as applied claims 1 and 27, respectively, but fail to teach wherein the capillary micropump comprises: a staggered array of microstructures.
However, Madadi teaches a self-driven microfluidic device (Fig. 1) including a transport channel followed by multiple plasma collected channels after the plasma flow branching from the transport channel through the MIMP filtration channel including an arrangement of diamond microposts to decrease the flow resistance and increase the capillary force (Fig. 1; col. 1, para. 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Sanders and Dimov by substituting the capillary micropump with the one including an arrangement of diamond microposts because it would decrease the flow resistance and increase the capillary force (Fig. 1; col. 1, para. 1).
Sanders, Dimov, and Madadi fail to teach the microstructures are substantially oval-shaped microstructures (for claims 5-6, 34).
However, Ding teaches using microstructure arrays ([Abstract]) for delivery of therapeutic agent (Title). The microstructures have a cross-dimensional shape selected from the group consisting of a diamond, a rectangular, and an oval (¶19).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Sanders, Dimov, and Madadi by substituting the diamond microposts with oval-shaped ones because microstructures of diamond or oval in shape are similar and suitable for delivery of therapeutic agent in microfluidic devices. Simple substitution of one known element for another to obtain predictable results is prima facie obvious. MPEP 2141(III)(B).
Claim(s) 17 and 21-26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sanders in view of Dimov, and further in view of Heikenfeld (US 2018/0317833).
Regarding claim 17, Sanders teaches a detection device, the detection device comprising:
a microfluidic passive sample separation device (Fig. 2: microfluidic passive plasma separation device 200) comprising:
a body (Fig. 2; ¶90: the body of device 200) defining an inlet (Fig. 2; ¶88: aperture 212) and an outlet (Fig. 2; ¶88: aperture 214), the body housing
a filter (Fig. 2; ¶92: an engineered filter pad 260) for filtering a liquid sample in contact therewith and for producing a filtrate (¶92: designed to retain the red and white blood cells and the platelets present in whole blood and allow only the plasma and its dissolved constituents to pass through);
a plurality of capillaries (Fig. 2; ¶101: a plurality of plasma collection channels 273) configured to withdraw the filtrate from the filter by capillary force (¶36: to a plasma collection reservoir by capillary force), each capillary having
a first end fluidly connected to the filter for receiving the filtrate (Fig. 2: indicating the plurality of capillary channels of 273 each having an end receiving the filtration passing through the filter pad 260); and
a second end (Fig. 2: the second ends of capillary channels 273 converging into the capillary 275).
Sanders further discloses the microfluidic capillary channel acts as a capillary pump, creating a lower pressure at the outlet of the engineered filter pad that accelerates the blood separation therethrough (¶9), which provide a sufficient pressure to overcome the capillary forces (¶38). Sanders does not explicitly disclose a capillary micropump fluidly connected to the second end of capillaries for dispensing the filtrate to the capillary pump; the capillary micropump being configured to receive the filtrate and to pump the filtrate to the outlet.
However, Dimov teaches a two-step, self-contained and self-powered
integrated microfluidic blood analysis system (SIMBAS) that integrates whole-blood plasma separation from red and white blood cells with multiple immunoassays (Fig. 1; p.846, col. 1, para. 3). The device includes suction chambers for fluid propulsion (Fig. 1), which regulates the total volume of plasma and stops the flow before the trench filters are overfilled (Fig. 1). Thus, the suction chambers are deemed to be a capillary micropump fluidly connected to the channels of plasma extraction and for dispensing the plasma.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Sanders by incorporating the suction chambers between the plurality of plasma collection channels and the outlet for generating a flow due to pressure difference as taught by Dimov because the suction chambers would be able to propels fluid and regulate the plasma volume and stop the flow before overfilled (Fig. 1) so that the device does not require any external support equipment with low-cost, high-volume manufacturing (p.846, col. 1, para. 3). Here, the claimed limitations are obvious because all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results. MPEP 2143(I)(A). The combined Sanders and Dimov would necessarily result in the capillary micropump between the end of capillaries and the outlet, and thus dispensing the filtrate from the end of capillaries to the micropump and then receiving and pumping the filtrate to the outlet.
Sanders further discloses the microfluidic passive plasma separation device is integrated directly to a point of care (POC) microfluidic diagnostic device (¶17), but fails to teach an electrochemical biosensor, the electrochemical biosensor fluidly coupled to the microfluidic passive sample separation device for detecting the analyte in the filtrate.
However, Heikenfeld teaches a fluid sensing device capable of collecting a fluid sample, concentrating the sample with respect to a target analyte, and measuring the target analyte in the concentrated sample (¶5). The fluid sample is a biofluid, including sweat, blood, and plasma (¶23), and the analyte-specific sensor is a sensor specific to the analyte and performs specific chemical recognition of the analyte’s presence or concentration, e.g., electrochemical aptamer-based sensors (¶41).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Sanders by incorporating an electrochemical biosensor for detecting the analyte in the separated plasma as taught by Heikenfeld because the electrochemical biosensor is a suitable biosensor for detect the presence of concentration of a target analyte. Here, the claimed limitations are obvious because all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results. MPEP 2143(I)(A).
The preamble “for detecting an analyte in a liquid sample” is deemed to be a statement with regard to the intended use and are not further limiting in so far as the structure of the product is concerned. In article claims, a claimed intended use must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. MPEP § 2111.02(II). The apparatus as taught by Sanders in view of Dimov and Heikenfeld is identical to the presently claimed structure and would therefore would have the ability to perform the use recited in the claim.
Regarding claim 21, the limitation “wherein the analyte comprises a nucleic acid, DNA, circulating DNA, high-risk HPV circulating DNA, high-risk HPV16 circulating DNA, a protein, an antibody, an antigen, a metabolite; a toxin; a biotoxin, such as domoic acid or okadaic acid; a small molecule; a cell; a bacterium; a virus; or an inflammatory marker, such as interleukins, cytokines, creative protein, pro-calcitonin, or pre-sepsin” is directed to a material or article worked upon. "Expressions relating the apparatus to contents thereof during an intended operation are of no significance in determining patentability of the apparatus claim." Ex parte Thibault, 164 USPQ 666, 667 (Bd. App. 1969). Furthermore, "[i]nclusion of material or article worked upon by a structure being claimed does not impart patentability to the claims." In re Young, 75 F.2d. 25 USPQ 69 (CCPA 1935) (as restated in In re Otto, 312 F.2d 937, 136 USPQ 458, 459 (CCPA 1963)). MPEP 2115.
Regarding claim 22, the limitation “wherein the liquid sample comprises blood; whole blood; urine; seminal fluid; vaginal fluid; tissue; an aqueous solution; marine or freshwater water; a marine or freshwater plant; marine or freshwater food; phytoplankton; shellfish; food; or milk; or a combination thereof” is directed to a material or article worked upon. "Expressions relating the apparatus to contents thereof during an intended operation are of no significance in determining patentability of the apparatus claim." Ex parte Thibault, 164 USPQ 666, 667 (Bd. App. 1969). Furthermore, "[i]nclusion of material or article worked upon by a structure being claimed does not impart patentability to the claims." In re Young, 75 F.2d. 25 USPQ 69 (CCPA 1935) (as restated in In re Otto, 312 F.2d 937, 136 USPQ 458, 459 (CCPA 1963)). MPEP 2115.
Regarding claim 23, Sanders teaches wherein the filtrate comprises plasma (¶2: separating plasma from whole blood).
Regarding claim 24, the designation “wherein the microfluidic passive filtration device is inverted” is deemed to be functional limitation in apparatus claims. MPEP 2114 (II). "[A]pparatus claims cover what a device is, not what a device does." Hewlett-Packard Co. v. Bausch & Lomb Inc., 909 F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990) (emphasis in original). A claim containing a "recitation with respect to the manner in which a claimed apparatus is intended to be employed does not differentiate the claimed apparatus from a prior art apparatus" if the prior art apparatus teaches all the structural limitations of the claim. Ex parte Masham, 2 USPQ2d 1647 (Bd. Pat. App. & Inter. 1987). Here, Sanders in view of Dimov teaches all structural limitations of the presently claimed microfluidic passive sample separation device and thus it is capable of being used inverted.
Regarding claim 25, Sanders teaches wherein the microfluidic passive sample separation device further comprising a capillary microchannel (Fig. 2; ¶101: first microfluidic capillary channel 275/277) and a capillary microwell housed in the body (Fig. 2: aperture 212 forming a microwell in the first layer 210),
the microchannel having a first end fluidly connected to the inlet for receiving the liquid sample (Fig. 2: the capillary channel 275 is fluidly connected to the aperture 212 for receiving the liquid sample), and a second end fluidly connected to the microwell for dispensing the liquid sample to the microwell (Fig. 2: the capillary channel 277 is fluidly connected to the microwell at the inlet), the microchannel configured to move the liquid sample from the inlet to the microwell by capillary force (¶36: to a plasma collection reservoir by capillary forces), and
the microwell having a first end fluidly connected to the microchannel for receiving the liquid sample (Fig. 2: indicating the top of the microwell is for receiving the sample and fluidly connected to capillary channels 275/277), and a second end coupled to the filter (Fig. 2: indicating the bottom of the microwell coupled to the filter pad 260).
The designation “the microwell configured to move the liquid sample from the microchannel to the filter by capillary force” is deemed to be functional limitation in apparatus claims. MPEP 2114 (II). "[A]pparatus claims cover what a device is, not what a device does." Hewlett-Packard Co. v. Bausch & Lomb Inc., 909 F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990) (emphasis in original). A claim containing a "recitation with respect to the manner in which a claimed apparatus is intended to be employed does not differentiate the claimed apparatus from a prior art apparatus" if the prior art apparatus teaches all the structural limitations of the claim. Ex parte Masham, 2 USPQ2d 1647 (Bd. Pat. App. & Inter. 1987). Here, Sanders in view of Dimov and Heikenfeld teaches all structural limitations of the presently claimed microfluidic passive sample separation device, including a microwell, and thus the microwell is capable of moving the liquid sample from the microchannel to the filter by capillary force.
Regarding claim 26, Sanders teaches wherein the detection device is suitable for point-of-care use (¶17).
Claim(s) 18-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sanders in view of Dimov and Heikenfeld, and further in view of Xiao (US 7,803,542).
Regarding claim 18, Sanders, Dimov, and Heikenfeld disclose all limitations of claim 17 as applied to claim 17. Sanders, Dimov, and Heikenfeld do not explicitly disclose wherein the electrochemical biosensor comprises a working electrode having a surface comprising a probe configured to couple to, bind to, or hybridize with the analyte.
However, Xiao teaches an aptamer-based detector (Col. 3, l.66) detecting a target that binds to a specific oligonucleotide sensor (Col. 6, ll.22-25), e.g., using aptamer selected or designed for specific binding purposes (Col. 6, ll.56-58). Here, the aptamer immobilized on the electrode surface (Fig. 1; Col. 3, ll.48-50: electrochemical detector based on the conformational change of the redox-labeled duplex DNA via target-induced strand displacement) is a probe configured to bind to the analyte (Fig. 1: target DNA).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Sanders, Dimov, and Heikenfeld by substituting the electrochemical biosensor with the one having a probe immobilized on the electrode surface and binding to the analyte as taught by Xiao because the electrochemical aptamer-based biosensor (EAB sensor) (Heikenfeld, ¶40, citing Xiao) is a suitable sensor to detect the presence of concentration of the target analyte in biofluid such as plasma (Heikenfeld, ¶23). Here, the claimed limitations are obvious because all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results. MPEP 2143(I)(A).
Regarding claim 19, Sanders, Dimov, Heikenfeld, and Xiao disclose all limitations of claim 18 as applied to claim 18. Sanders, Dimov, and Heikenfeld do not explicitly disclose wherein the working electrode is a gold-based electrode.
However, Xiao teaches the electrode comprises a metal, such as gold (Col. 3, ll.16-17).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Sanders, Dimov, and Heikenfeld by substituting the electrode with one formed from gold as taught by Xiao. The suggestion for doing so would have been that gold is a suitable material for electrode of and EAB sensor and the selection of a known material, which is based upon its suitability for the intended use, is within the ambit of one of ordinary skill in the art. MPEP § 2144.07.
Claim(s) 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sanders in view of Dimov, Heikenfeld and Xiao, and further in view of Dong (US 11,022,610).
Regarding claim 20, Sanders, Dimov, Heikenfeld, and Xiao disclose all limitations of claim 18 as applied to claim 18. Sanders, Dimov, Heikenfeld, and Xiao do not explicitly disclose wherein the probe is immobilized on the working electrode by drop-cast graphene oxide (GO) on the surface of the working electrode and a covalent bond formed between the probe and the GO.
However, Dong teaches a microfluidic sensor chip using a patterned periodic array of nanoposts coated with a noble metal and graphene oxide (GO) to detect target biomarker for electrochemical sensing ([Abstract]). The gold (Au) nanopost array was drop-coated with a layer of GO nanosheets to enable covalent conjugation of anti-ErbB2 that on the surface of nanoposts (Col. 11, ll.10-12; Col. 9, l.63). Thus, Dong teaches the probe (anti-ErbB2) is immobilized on the working electrode (Au nanopost array) by drop-cast graphene oxide (GO) on the surface of the working electrode and a covalent bond formed between the probe and the GO (Col. 11, ll.10-12).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Sanders, Dimov, Heikenfeld, and Xiao by incorporating graphene oxide (GO) to form a covalent bond between the probe and the GO as taught by Dong because graphene oxide assembled on the surface of the Au-coated nanoposts would facilitate biofunctionalization with antibody molecules (Col. 24, ll.15-17). Here, the claimed limitations are obvious because all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results. MPEP 2143(I)(A).
The limitation “and the probe is optionally a complementary single stranded DNA (cssDNA)” is optional and not required in the prior art.
Claim(s) 30 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sanders in view of Dimov, and further in view of Benn (US 2008/0217246).
Regarding claim 30, Sanders and Dimov discloses all limitations of claim 1 as applied claim 1, but fails to teach wherein the outlet comprises a series of outlet reservoirs.
However, Benn teaches an electrochemical detection system having a cartridge capable of performing a plurality of assay protocols ([Abstract]). The electrochemical detection system includes a plurality of flow cells that receive the same sample for performing the plurality of assay protocols, i.e., simultaneously performing on a single cartridge as well as a single sample for multiple analytes (¶10). The extracted plasma from the whole blood sample is stored in the sample reservoir for controlled release to a plurality of flow cells contained within the cartridge (¶14).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Sanders and Dimov by incorporating a series of outlet reservoirs as taught by Benn because the series of outlet reservoirs, e.g., the plurality of flow cells, would provide the same plasma sample to be analyzed for multiple analyte simultaneously (¶10). Here, the claimed limitations are obvious because all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results. MPEP 2143(I)(A).
Response to Arguments
Applicant’s arguments have been considered but are unpersuasive.
Applicant argues Sanders relies on capillary forces to move filtered plasma through the device, which facilitate the movement of fluids through narrow spaces via adhesive and cohesive forces, while Dimov relies on pressure differentials (i.e., suction forces) to move whole blood through the device, not capillary forces (p. 14, para. 3-4). This argument is unpersuasive. Although Sanders does not teach an additional capillary micropump downstream of the second of the plurality of capillaries, it explicitly discloses the microfluidic capillary channel acts as a capillary pump, creating a lower pressure at the outlet of the engineered filter pad that accelerates the blood separation therethrough (¶9), which provide a sufficient pressure to overcome the capillary forces (¶38). Thus, the capillary force, e.g., adhesive and cohesive forces as argued, would be resistance for the flow to go through narrow spaces. The flow can be generated only when there is a sufficient pressure to overcome the capillary forces, e.g., a higher pressure at the inlet end or a lower pressure (by suction) at the outlet end. Dimov discloses a suction chambers downstream from the plasma extraction and biomarker detection, which is a capillary micropump that provides for fluid propulsion. Since both references disclose a generated flow through microfluidic channels based on a sufficient pressure to overcome capillary forces, they are analogous art and would be obvious to one of ordinary skill in the art to combine them to arrive the claimed invention.
Applicant argues Dimov teaches a closed device without any outlets (p. 14, last para.), and thus the modification as taught by Dimov would change the principle of operation of the Sanders device (p. 15, para. 1). Applicant also argues the combination would have had to further modify the Sanders device into a closed system (p. 15, para. 2). These arguments are unpersuasive. Sanders device is an open system with inlet and outlet, and Dimov’s suction chamber functions as a capillary micropump for generating flow inside the microchannels based on sufficient pressure difference that overcomes capillary forces. Thus, the incorporation of Dimov’s suction chamber downstream of the microchannel and between its inlet and outlet of Sanders device would not change its principle of operation or be unsatisfactory for its intended purpose. As disclosed by Sanders, by creating a lower pressure at the outlet side would provide a sufficient pressure to overcome the capillary forces, which is equivalent to apply a suction force as the suction chamber of Dimov.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CAITLYN M SUN whose telephone number is (571)272-6788. The examiner can normally be reached M-F: 8:30am - 5:30pm.
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