DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
Claims 1-9, and 11-17 are pending and under examination.
Claim 10 has been canceled.
Response to Amendment
Applicants amendments to the claims received on 08/20/2026 have overcome the claim objection(s), 112(b) rejection(s), and 112(d) rejection(s) previously set forth in the Non-Final Office Action mailed on 04/20/2026. However, based on the claim amendments, new claim objections have been set forth.
Based on the amended claims and remarks, the previous prior art rejection over Glezer has been modified to address the amended claims (see below).
Claim Objections
Claim 14 is objected to because of the following informalities:
Claim 14 line 4 recites “a blood sample”, line 9 recites “a working fluid”, and lines 12-13 recite “a liquid meniscus”. However, claim 1, from which claim 14 depends, has also been amended to recite “a blood sample” in line 2, “a working fluid” in line 9, and “a liquid meniscus” in lines 15-16. The examiner requests applicant amend claim 14 to refer to “the blood sample”, “the working fluid”, and “the liquid meniscus” in each instance.
Appropriate correction is required.
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 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 1-9, 11 and 14-17 and are rejected under 35 U.S.C. 103 as being unpatentable over Glezer et al. (US 2004/0189311; already of record – hereinafter “Glezer”), in view of Davis et al. (US 2007/0031283; already of record – hereinafter “Davis”) and Chen et al. (US 2019/0336967; already of record – hereinafter “Chen”).
Regarding claim 1, Glezer disclose a microfluidic device (Glezer; fig. 25, #2500, [0264]) comprising:
A. a blood sample inlet adapted to receive a blood sample (Glezer; fig. 25, #2510, [0186, 0272]);
B. a separation membrane proximal to the sample inlet (Glezer; [0186]);
C. a manifold inlet in fluid connection with the blood sample inlet at a junction, said manifold inlet being adapted to receive a working fluid (Glezer disclose a junction where conduits from the sample chamber 2510 and reagent chambers A/B intersect, a manifold connects with the junction to allow reagents A/B to be received; fig. 25);
D. a pump in fluid connection with and downstream of the junction (Glezer disclose a pump (fig. 24) in fluid connection with waste vents A/B 2442A (corresponding to 2542A in fig. 25) & 2442B (corresponding to 2542B in fig. 25) of waste chambers 2540A/2540B downstream of the junction; figs. 24-26, [0272-0277]); and
E. an air vent in fluid connection with the pump (Glezer disclose a pump (fig. 24) in fluid connection with waste vents A/B 2442A (corresponding to 2542A in fig. 25) & 2442B (corresponding to 2542B in fig. 25) of waste chambers 2540A/2540B downstream of the junction; figs. 24-26, [0272-0277]), wherein the separation membrane is positioned between the blood sample inlet and the junction (Glezer; [0186]); and
wherein, in operation, at least due to the difference between the pressure at the manifold inlet, the pressure at the blood sample inlet and the pressure at the junction, a liquid meniscus of a blood sample at the blood sample inlet is adapted to be drained first, and a liquid meniscus of a working fluid at the manifold inlet is adapted to move only when the blood sample at the blood sample inlet is substantially completed drained (Glezer disclose air vents and pump to create positive and negative pressure throughout defined channels of the microfluidic device, where sample flows from the sample inlet, past the manifold inlet, and through the junction when drawn towards sensor 3; figs. 25-26, [0272-0277]. Accordingly, a driving pressure (high pressure) at the sample inlet pushes the sample fluid past the manifold inlet through the junction towards sensor 3. Glezer further disclose z-transition 1011 in the sample conduit and 1013 in the reagent conduit that act as capillary breaks which confine sample liquids and reagent liquids to their corresponding chambers. Fluids can be moved from these chambers, in a controlled and reproducible manner, by application of an appropriate pressure gradient; fig. 10, [0231]).
Note: The difference in pressure between the manifold inlet, blood sample inlet, and the junction relates to function/intended use. However, functional language does not add any further structure to an apparatus beyond that of a capability. Apparatus claims must distinguish over the prior art in terms of structure rather than function (see MPEP 2114 and 2111.04). Therefore, if the prior art structure is capable of performing the function, then the prior art meets the limitation in the claims.
Glezer does not teach the separation membrane comprising: i. a top layer proximal to the blood sample inlet, the top layer having an average pore size of from 1 µm to 50 µm in diameter; and ii. a bottom layer distal from the blood sample inlet, the bottom layer having an average pore size of from 0.05 µm to 20 µm in diameter.
However, Davis teach the analogous art of a microfluidic device (Davis; fig. 20a, [0044, 0280]) comprising a blood sample inlet (Davis; figs. 20a, #2000, [0280]) and a separation membrane (Davis; fig. 20a, #2002, [0280]) wherein the separation membrane comprises a top layer proximal to the blood sample inlet, the top layer having an average pore size of from 1 µm to 50 µm in diameter; and ii. a bottom layer distal from the blood sample inlet, the bottom layer having an average pore size of from 0.05 µm to 20 µm in diameter (Davis disclose the separation membrane may be an asymmetric pore membrane blood separation filter that has the pores change size across the thickness of the filter where one side would have larger pores that gradually change to smaller pores to generate plasma from whole blood samples; [0251]. The filter 2002 can have different pore size rating depending on the embodiment and intended use which include which include 0.05, 0.1, 0.2, 0.5,1, 2, 3, 4, 7, 10, 15, 20, 50, or 100 µm to remove interfering components of the sample matrix; [0248-249]).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the separation membrane of Glezer with the separation member having a top layer and a bottom layer, as taught by Davis, because Davis teach the separation member having a top layer and a bottom layer has pores that change size across the thickness of the filter where one side would have larger pores that gradually change to smaller pores to generate plasma from whole blood samples; [0251]. One of ordinary skill in the art would have expected this modification could have been performed with a reasonable expectation of success since Glezer and Davis both teach processing blood samples in a microfluidic cartridge.
Modified Glezer does not teach the pump is a capillary pump.
However, Chen teach the analogous art of a microfluidic device (Chen; fig. 1, #100, [0047]) comprising a pump and an air vent (Chen; fig. 1, #110, #112, [0048]) wherein the pump is a capillary pump (Chen; [0048]).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the pump of modified Glezer with the capillary pump, as taught by Chen, because Chen teach the capillary pump moves the sample solution from an inlet 102 through the microfluidic device by liquid wicking until the capillary pump is fully filled, ensuring a consistent volume filling through the microfluidic device thereby minimizing fluctuations and errors in measurement (Chen; 0048, 0051]). One of ordinary skill in the art would have expected this modification could have been performed with a reasonable expectation of success since modified Glezer and Chen both teach processing a sample using separation methods in a microfluidic device.
Regarding claim 2, modified Glezer teach the microfluidic device according to claim 1 above, wherein the average pore size of the top layer is from 3 µm to 20 µm in diameter and the average pore size of the bottom layer is from 0.1 µm to 7 µm in diameter (The modification of the separation membrane of Glezer with the separation member having a top layer and a bottom layer, as taught by Davis, has previously been discussed in claim 1 above. Davis teach the filter 2002 can have different pore size rating depending on the embodiment and intended use which include 0.05, 0.1, 0.2, 0.5,1, 2, 3, 4, 7, 10, 15, 20, 50, or 100 µm to remove interfering components of the sample matrix; [0248-249]).
Regarding claim 3, modified Glezer teach the microfluidic device according to claim 1 above, wherein the separation membrane further comprises an additional layer, and wherein the additional layer is located proximal to the sample inlet and above the top layer (The modification of the separation membrane of Glezer with the separation member having a top layer and a bottom layer, as taught by Davis, has previously been discussed in claim 1 above. Davis teach the pores change size across the thickness of the filter where one side would have larger pores that gradually change to smaller pores to generate plasma from whole blood samples; [0251]).
Regarding claim 4, modified Glezer teach the microfluidic device according to claim 3 above, wherein the additional layer has a pore size of from 20 µm to 100 µm in diameter (The modification of the separation membrane of Glezer with the separation member having a top layer and a bottom layer, as taught by Davis, has previously been discussed in claim 1 above. Davis teach the pores change size across the thickness of the filter where one side would have larger pores that gradually change to smaller pores to generate plasma from whole blood samples; [0251]. The filter 2002 can have different pore size rating depending on the embodiment and intended use which include 0.05, 0.1, 0.2, 0.5,1, 2, 3, 4, 7, 10, 15, 20, 50, or 100 µm to remove interfering components of the sample matrix; [0248-249]).
Regarding claim 5, modified Glezer teach the microfluidic device according to claim 1 above, further comprising a reaction chamber to detect a biomarkers in extracted plasma in fluid connection with the separation membrane, wherein the reaction chamber is downstream of the separation membrane (Glezer; fig. 25, #2550A/B, [0186, 0274, 0278]).
Regarding claim 6, modified Glezer teach the microfluidic device according to claim 5 above, wherein the biomarker is selected from the group consisting of alpha fetoprotein, a SARS CoV-2 antibody, a SARS CoV-2 antigen, serum albumin, prostate-specific antigen, blood creatinine, blood cystatin C, and a combination thereof (Glezer; [0122]).
Regarding claim 7, modified Glezer teach the microfluidic device according to claim 5 above, wherein the reaction chamber comprises a capture mechanism selected from the group consisting of an immobilized antibody, an immobilized antigen, immobilized microparticles, and a combination thereof (Glezer; [0276, 0278]).
Regarding claim 8, modified Glezer teach the microfluidic device according to claim 5 above, wherein the reaction chamber contains a reactant for a reaction selected from the group of a color reaction, an antibody reaction, an enzymatic reaction, an electrochemical reaction, fluorescence, chemiluminescence, and a combination thereof (Glezer; [0278]).
Regarding claim 9, modified Glezer teach the microfluidic device according to claim 7 above, wherein the reaction chamber contains a reactant for a reaction selected from the group of a color reaction, an antibody reaction, an enzymatic reaction, an electrochemical reaction, fluorescence, chemiluminescence, and a combination thereof (Glezer; [0278]).
Regarding claim 11, modified Glezer teach the microfluidic device according to claim 1, wherein the capillary pump is selected from the group consisting of a porous-material-based capillary pump, a single microchannel with a hydrophilic surface, a multiple microchannel with a hydrophilic surface, a chamber with a hydrophilic microstructure, and a combination thereof (The modification of the pump of modified Glezer with the capillary pump, as taught by Chen, has previously been discussed in claim 1 above. Chen additionally disclose the micro-channels are hydrophilic; [0015, 0019, 0051]).
Regarding claim 14, modified Glezer teach a method for separating blood plasma from a blood sample (Glezer; fig. 16, [0186, 0271-0277])comprising the steps of:
A. providing the microfluidic device according to claim 1, wherein the air vent is either a closed air vent or opened air vent (The microfluidic device according to claim 1 has previously been discussed above. Glezer teach the waste vents A/B 2442A (corresponding to 2542A in fig. 25) & 2442B (corresponding to 2542B in fig. 25) of waste chambers 2540A/2540B are opened to aspirate/draw sample from the sample chamber 2510; [0272]);
B. providing a blood sample comprising a plurality of red blood cells and blood plasma therein (Glezer; [0186, 0272]);
C. adding the blood sample to the blood sample inlet (Glezer; [0186, 0272]);
D. allowing the blood sample to flow from the blood sample inlet to the separation membrane (Glezer teach the waste vents A/B 2442A (corresponding to 2542A in fig. 25) & 2442B (corresponding to 2542B in fig. 25) of waste chambers 2540A/2540B are opened to aspirate/draw sample from the sample chamber 2510; [0272]);
E. filtering the red blood cells from the blood plasma (Glezer; [0186]);
F. adding a working fluid to the manifold inlet (Glezer; [0275]);
G. extracting the blood plasma separated by the separation membrane via sequential draining (Glezer; [0186, 0274]);
wherein, at least due to the difference between the pressure at the manifold inlet, the pressure at the blood sample inlet and the pressure at the junction, a liquid meniscus of the blood sample at the blood sample inlet is drained first, and a liquid meniscus of the working fluid at the manifold inlet moves only when the blood sample at the blood sample inlet is substantially completely drained (Glezer disclose air vents and pump to create positive and negative pressure throughout defined channels of the microfluidic device, where sample flows from the sample inlet, past the manifold inlet, and through the junction when drawn towards sensor 3; figs. 25-26, [0272-0277]. Accordingly, a driving pressure (high pressure) at the sample inlet pushes the sample fluid past the manifold inlet through the junction towards sensor 3. Glezer further disclose z-transition 1011 in the sample conduit and 1013 in the reagent conduit that act as capillary breaks which confine sample liquids and reagent liquids to their corresponding chambers. Fluids can be moved from these chambers, in a controlled and reproducible manner, by application of an appropriate pressure gradient; fig. 10, [0231]).
Note: The difference in pressure between the manifold inlet, blood sample inlet, and the junction relates to function/intended use. However, functional language does not add any further structure to an apparatus beyond that of a capability. Apparatus claims must distinguish over the prior art in terms of structure rather than function (see MPEP 2114 and 2111.04). Therefore, if the prior art structure is capable of performing the function, then the prior art meets the limitation in the claims.
Regarding claim 15, modified Glezer teach the method for separating blood plasma from a blood sample according to claim 14, wherein the blood plasma flows from the separation membrane downstream to the capillary pump (The modification of the pump of modified Glezer with the capillary pump, as taught by Chen, has previously been discussed in claim 1 above. Glezer teach the blood plasma flows from the separation membrane at the sample chamber inlet 2510 downstream to the pump connected to waste air vent 2442A/B; fig. 16, [0271-0277]).
Regarding claim 16, modified Glezer teach the microfluidic device according to claim 1 above, wherein, during operation, the pressure at the blood sample inlet is larger than the pressure at the junction, which is in turn larger than the pressure at the manifold inlet (Glezer disclose air vents and pump to create positive and negative pressure throughout defined channels of the microfluidic device, where sample flows from the sample inlet, past the manifold inlet, and through the junction when drawn towards sensor 3; figs. 25-26, [0272-0277]. Glezer further disclose z-transition 1011 in the sample conduit and 1013 in the reagent conduit that act as capillary breaks which confine sample liquids and reagent liquids to their corresponding chambers. Fluids can be moved from these chambers, in a controlled and reproducible manner, by application of an appropriate pressure gradient; fig. 10, [0231]. Thus, a driving pressure is generated at the sample inlet, which is larger than the pressure at the junction, which is in turn larger than a pressure at the z-transition of the manifold to maintain separation between the fluids).
Note: The difference in pressure between the manifold inlet, blood sample inlet, and the junction relates to function/intended use. However, functional language does not add any further structure to an apparatus beyond that of a capability. Apparatus claims must distinguish over the prior art in terms of structure rather than function (see MPEP 2114 and 2111.04). Therefore, if the prior art structure is capable of performing the function, then the prior art meets the limitation in the claims.
Regarding claim 17, modified Glezer teach the method of claim 14 above, wherein the pressure at the blood sample inlet is larger than the pressure at the junction (Glezer disclose air vents and pump to create positive and negative pressure throughout defined channels of the microfluidic device, where sample flows from the sample inlet, past the manifold inlet, and through the junction when drawn towards sensor 3; figs. 25-26, [0272-0277]. Glezer further disclose z-transition 1011 in the sample conduit and 1013 in the reagent conduit that act as capillary breaks which confine sample liquids and reagent liquids to their corresponding chambers. Fluids can be moved from these chambers, in a controlled and reproducible manner, by application of an appropriate pressure gradient; fig. 10, [0231]. Thus, a driving pressure is generated at the sample inlet, which is larger than the pressure at the junction, which is in turn larger than a pressure at the z-transition of the manifold to maintain separation between the fluids).
Note: The difference in pressure between the manifold inlet, blood sample inlet, and the junction relates to function/intended use. However, functional language does not add any further structure to an apparatus beyond that of a capability. Apparatus claims must distinguish over the prior art in terms of structure rather than function (see MPEP 2114 and 2111.04). Therefore, if the prior art structure is capable of performing the function, then the prior art meets the limitation in the claims.
Claims 12-13 and are rejected under 35 U.S.C. 103 as being unpatentable over Glezer in view of Davis and Chen, and further in view of Seelig et al. (US 2013/0071839; already of record – hereinafter “Seelig”).
Regarding claim 12, modified Glezer teach the microfluidic device according to claim 1 above.
Modified Glezer does not teach wherein the capillary pump comprises a filter.
However, Seelig teach the analogous art of a microfluidic device (Seelig; fig. 7, [0064]), wherein the microfluidic device comprise a sample inlet and a capillary pump (Seelig disclose a paper-based microfluidic device comprising filter paper to wick fluids by capillary action; fig. 15, [0065, 0112]), wherein the capillary pump comprise a filter (Seelig; [0065]).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the capillary pump of modified Glezer to comprise filter paper, as taught by Seelig, because Seelig teach the filter paper capillary pump allows delivery of multiple fluids to a detection zone in a timed sequence (Seelig; [0016]). One of ordinary skill in the art would have expected this modification could have been performed with a reasonable expectation of success since modified Glezer and Seelig both teach transporting a fluid sample through a microfluidic device using a capillary pump.
Regarding claim 13, modified Glezer teach the microfluidic device according to claim 12 above, wherein the filter comprises cellulose, cotton linter, and a combination thereof (The modification of the capillary pump of modified Glezer to comprise filter paper, as taught by Seelig, has previously been discussed in claim 12 above. Seelig disclose the filter comprises cellulose; [0065]).
Response to Arguments
Applicants arguments, filed 08/20/2026, have been considered but are moot because the arguments are towards the amended claims and do not apply to the current grounds of rejection. However, because the examiner is using the same prior art in the rejection, then the examiner will address applicant’s remarks in order to promote compact prosecution.
Applicants argue on pages 7-8 of their remarks, that the cited references do not disclose or suggest the sequenced-drainage arrangement, in which the relative pressures at the sample inlet, junction, and manifold inlet are configured so that the blood sample is drained to completion before the working fluid begins to move. The examiner respectfully disagrees. Glezer disclose air vents and pump to create positive and negative pressure throughout defined channels of the microfluidic device, where sample flows from the sample inlet, past the manifold inlet, and through the junction when drawn towards sensor 3; figs. 25-26, [0272-0277]. Accordingly, a driving pressure (high pressure) at the sample inlet pushes the sample fluid past the manifold inlet through the junction towards sensor 3. Glezer further disclose z-transition 1011 in the sample conduit and 1013 in the reagent conduit that act as capillary breaks which confine sample liquids and reagent liquids to their corresponding chambers. Fluids can be moved from these chambers, in a controlled and reproducible manner, by application of an appropriate pressure gradient; fig. 10, [0231]. Lastly, the difference in pressure between the manifold inlet, blood sample inlet, and the junction relates to function/intended use. However, functional language does not add any further structure to an apparatus beyond that of a capability. Apparatus claims must distinguish over the prior art in terms of structure rather than function (see MPEP 2114 and 2111.04). Therefore, if the prior art structure is capable of performing the function, then the prior art meets the limitation in the claims.
Citations to art
In the above citations to documents in the art, an effort has been made to specifically cite representative passages, however rejections are in reference to the entirety of each document relied upon. Other passages, not specifically cited, may apply as well.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CURTIS A THOMPSON whose telephone number is (571)272-0648. The examiner can normally be reached on M-F: 7:00 a.m. - 5:00 p.m..
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E-mail communication Authorization
Per updated USPTO Internet usage policies, Applicant and/or applicant’s representative is encouraged to authorize the USPTO examiner to discuss any subject matter concerning the above application via Internet e-mail communications. See MPEP 502.03. To approve such communications, Applicant must provide written authorization for e-mail communication by submitting the following statement via EFS Web (using PTO/SB/439) or Central Fax (571-273-8300):
Recognizing that Internet communications are not secure, I hereby authorize the USPTO to communicate with the undersigned and practitioners in accordance with 37 CFR 1.33 and 37 CFR 1.34 concerning any subject matter of this application by video conferencing, instant messaging, or electronic mail. I understand that a copy of these communications will be made of record in the application file.
Written authorizations submitted to the Examiner via e-mail are NOT proper. Written authorizations must be submitted via EFS-Web (using PTO/SB/439) or Central Fax (571-273-8300). A paper copy of e-mail correspondence will be placed in the patent application when appropriate. E-mails from the USPTO are for the sole use of the intended recipient, and may contain information subject to the confidentiality requirement set forth in 35 USC § 122. See also MPEP 502.03.
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/C.A.T./Examiner, Art Unit 1798
/BENJAMIN R WHATLEY/Primary Examiner, Art Unit 1798
