Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 06/09/26 has been entered.
Response to Amendment
Applicant’s amendment and remark filed on 06/09/26 have been entered. Claims 1-6 and 8 remain pending. Claim 8 remain withdrawn. Claims 1-6 are examined herein.
Response to Arguments
Applicant’s arguments, see pages 6-9, filed 06/09/26, with respect to the rejection(s) of claim(s) 1-6 under 103 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Tamiya (WO 2006016117 A1).
The amendment requires the calibration curve liquid to be prefilled, stored, and sealed in the plurality of first channels while leaving the final channel open for receiving a measurement/sample fluid. This limitation is not explicitly taught in the previous rejection of Wakao in view of Ren. Upon additional searching and consideration, Examiner believes the prior art, Tamiya, would have cured the deficiency introduced by the new limitation. Tamiya (See rejection below) requires the manufacturing of a microfluidic device in a specific order. Tamiya requires calibration curve liquids with different concentrations to be filled in a plurality of microchannels before a final sample solution can be filled and occupied the last remaining microchannel (para. [0043]-[0044]). See the rejection below.
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) 1-3 and 5-6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wakao (High-throughput fluorescence polarization immunoassay by using a portable fluorescence polarization imaging analyzer, 2019) in view of Ren (Reconfigurable Acrylic-tape Hybrid Microfluidics, 2019) as cited in previous Office Action and Tamiya (WO 2006016117 A1).
Regarding claim 1, Wakao discloses a microdevice (PDMS-glass microdevice) (Figure 4), comprising:
a plurality of calibration curve liquids including a measurement target substance of a predetermined concentration, the predetermined concentration in each of the plurality of calibration curve liquids being mutually different (The DON (deoxynivalenol) standard was diluted to 8 different concentrations (2.4, 4.8, 9.6, 19.2, 38.5, 76.9, 153.8, and 615.4 ng mL−1 )) (Chemicals, 2583), an antibody that specifically binds to the measurement target substance (anti-DON antibodies) (Chemicals, 2583), and a fluorescent-labeling derivative that fluorescently labels the measurement target substance and competes with the measurement target substance to specifically bind to the antibody (fluorescein-conjugated DON) (Chemicals, 2583);
a first substrate member (glass slide) (the microdevice design had been transferred to, was pasted on a glass slide) (2584, Fabrication of the PDMS-glass microdevice, left col.; Figure 4);
a second substrate (the clear PDMS or black PDMS microdevice, Figure 4) facing the first substrate;
a partition wall sandwiched between the first substrate and the second substrate (Figure 5A; see below);
PNG
media_image1.png
656
717
media_image1.png
Greyscale
a plurality of first microchannels defined by the partition wall, each having an opening penetrating the second substrate and the partition wall, extending linearly (See annotated Figure 5A above), and respectively filled with the plurality of calibration curve liquids (the microdevice had eight microchannels, each with an individual inlet and outlet, and could hold eight different samples) (Fabrication of the PDMS-glass microdevice, 2584; Figure 5); and
at least one second microchannel, the at least one second microchannel being defined by the partition wall (the microdevice had eight microchannels, each with an individual inlet and outlet, and could hold eight different samples) (Fabrication of the PDMS-glass microdevice, 2584; Figure 5) (Each microchannel had twelve microchambers to realize measurement of the 96 [mycotoxins] samples) (Fabrication of the PDMS-glass microdevice, 2584; Figures 5 and 6). (The limitation, “to be filled with a measurement target liquid including a measurement target substance, the antibody, and the fluorescent-labeling derivative”, is interpreted as a recitation of intended use).
Wakao does not disclose a sealing member that seals the plurality of calibration curve liquids in the plurality of first microchannels by closing the opening of each of the plurality of first microchannels with the plurality of first microchannels being respectively filled with the plurality of calibration curve liquids. Wakao also does not disclose storing the respective one of the plurality of calibration curve liquids in the plurality of first channels in advance.
In an analogous art, Ren discloses a hydrophobic, single-sided tape used to seal the inlet and outlet of acrylic microfluidic chip (Figure 4a).
In another analogous art, Tamiya discloses a device (12, Fig. 7) for quantifying substance by fluorescence (20, Fig. 3) comprising:
a plurality of microchannels (13, Fig. 7) to be filled with calibration curve or sample fluid.
Tamiya discloses the at least ten of the microchannels are reserved for creating a calibration curve, and the remaining one is a microchannel for receiving sample solution (Ten of the microchannel 13 is a microchannel for creating a calibration curve, and the remaining one is a microchannel for the sample solution. Para. [0043]). Furthermore, Tamiya discloses the manufacturing of the device requires calibration solution to be filled in to the channels first before sample solution are allowed to be introduced to the last channel (…sample discharge unit 16 are closed in advance. Then, the tube corresponding to any one of the minute flow passages 13 is opened, and a standard substance solution of a predetermined concentration for creating a calibration curve is made to flow from the sample introduction part 15, for example, to perform measurement. When a solution for preparing another calibration curve or a reagent solution is measured, the process is repeated for each microchannel 13. By forming the plurality of fine passages 13 on the chip, the calibration curve can be created on one chip and the concentration of the measurement target substance in the sample can be easily measured. Para. [0044]).
PNG
media_image2.png
538
279
media_image2.png
Greyscale
As the method of Tamiya implies an order in which calibration curve liquids are expected to be filled in before introduction of sample fluid, it would have been obvious to one of ordinary skilled in the art to have incorporated a tape layer such as the one taught by Ren to seal off the opening of the first microfluidic channels of Wakao while leaving the final channel open for sample fluid comprising target substance of unknown concentration, antibody, and a fluorescent label. Doing so comes with the benefits of preventing leaks and maintaining enclosed fluid paths and preventing contamination of the calibration curve liquid while also allowing the device to be transport and portable before an actual sample fluid is being filled into the last channel. In reLindberg, 194 F.2d 732, 93 USPQ 23 (CCPA 1952) (Fact that a claimed device is portable or movable is not sufficient by itself to patentably distinguish over an otherwise old device unless there are new or unexpected results.).
Regarding claim 2, Modified Wakao discloses the claimed invention as discussed above claim 1. Ren discloses the sealing member is a water repellant (hydrophobic tape).
Regarding claim 3, Modified Wakao discloses the claimed invention as discussed above claim 1. Ren discloses the sealing member is an EL-92734 tape from Adhesives Research (Tape sealing of the acrylic channels), which includes a base material that is flexible (giving “flexible” its broadest reasonable interpretation, tape has a degree of flexibility) and an adhesive layer that is water repellant (the paste is interpreted as an adhesive and Ren discloses the tape ).
Regarding claim 5, Modified Wakao teaches the invention as discussed above in claim 1. Wakao does not teach the coefficient of determination to be greater than 0.99. A result effective variable is one that has well known and expected results. It is well known within the art that the coefficient of determination increases with additional data points and has the advantage of increasing the certainty of the data. It would have been obvious to modify Wakao and increase the coefficient of determination to be greater than 0.99 to achieve the well known and expected results of increasing the certainty of the data as optimization of a result effective variable.
Regarding claim 6, Wakao discloses a method of manufacturing a microdevice comprising:
Forming, from a first substrate (glass slide), a second substrate (PDMS), and a partion wall sandwiched between the first substrate and the second substrate (see annotated Figure 5A above) a plurality of first microchannels (the microdevice had eight microchannels, each with an individual inlet and outlet, and could hold eight different samples) (Fabrication of the PDMS-glass microdevice, 2584; Figure 5), and at least one second microchannel (the microdevice had eight microchannels, each with an individual inlet and outlet, and could hold eight different samples) (Fabrication of the PDMS-glass microdevice, 2584; Figure 5) to be filled with a measurement target liquid of a measurement target substance, an antibody that specifically binds to the measurement target substance (anti-DON antibodies) (Chemicals, 2583), and a fluorescent-labeling derivative that fluorescently labels (fluorescein-conjugated DON) (Chemicals, 2583) the measurement target substance and competes with the measurement target substance to specifically bind to the antibody;
filling the plurality of first microchannels respectively with a plurality of calibration curve liquids including the measurement target substance of a predetermined concentration (The DON (deoxynivalenol) standard was diluted to 8 different concentrations (2.4, 4.8, 9.6, 19.2, 38.5, 76.9, 153.8, and 615.4 ng mL−1 )) (Chemicals, 2583) through an opening of the microchannels, the predetermined concentration in each of the plurality of calibration curve liquids being mutually different, the antibody (anti-DON antibodies) (Chemicals, 2583), and the fluorescent-labeling derivative (fluorescein-conjugated DON) (Chemicals, 2583).
Wakao does not disclose sealing the plurality of calibration curve liquids by closing, by a sealing member, the opening of each of the plurality of first microchannel with the plurality of first microchannels being respectively with the plurality of calibration curve liquids, and storing a plurality of calibration curve liquids.
In an analogous art, Ren discloses applying hydrophobic, single-sided tape used to seal the inlet and outlet of acrylic microfluidic chip (Figure 5).
In another analogous art, Tamiya discloses a device (12, Fig. 7) for quantifying substance by fluorescence (20, Fig. 3) comprising:
a plurality of microchannels (13, Fig. 7) to be filled with calibration curve or sample fluid.
Tamiya discloses the at least ten of the microchannels are reserved for creating a calibration curve, and the remaining one is a microchannel for receiving sample solution (Ten of the microchannel 13 is a microchannel for creating a calibration curve, and the remaining one is a microchannel for the sample solution. Para. [0043]). Furthermore, Tamiya discloses the manufacturing of the device requires calibration solution to be filled in to the channels first before sample solution are allowed to be introduced to the last channel (…sample discharge unit 16 are closed in advance. Then, the tube corresponding to any one of the minute flow passages 13 is opened, and a standard substance solution of a predetermined concentration for creating a calibration curve is made to flow from the sample introduction part 15, for example, to perform measurement. When a solution for preparing another calibration curve or a reagent solution is measured, the process is repeated for each microchannel 13. By forming the plurality of fine passages 13 on the chip, the calibration curve can be created on one chip and the concentration of the measurement target substance in the sample can be easily measured. Para. [0044]).
As the method of Tamiya implies an order in which calibration curve liquids are expected to be filled in before introduction of sample fluid, it would have been obvious to one of ordinary skilled in the art to have incorporated a tape layer such as the one taught by Ren to seal off the opening of the first microfluidic channels of Wakao. Doing so comes with the benefits of preventing leaks and maintaining enclosed fluid paths and preventing contamination of the calibration curve liquid while also allowing the device to be transport and portable before an actual sample fluid is being filled into the last channel. In reLindberg, 194 F.2d 732, 93 USPQ 23 (CCPA 1952) (Fact that a claimed device is portable or movable is not sufficient by itself to patentably distinguish over an otherwise old device unless there are new or unexpected results.).
Claim 4 is rejected under 35 U.S.C. 103 as being obvious over Wakao in view of Ren and Tamiya as discussed above in claim 1, and further in view of Kho (Biosensor Technology Reveals the Disruption of the Endothelial Barrier Function and the Subsequent Death of Blood Brain Barrier Endothelial Cells to Sodium Azide and Its Gaseous Products, 2017) as cited in previous OA.
Regarding claim 4, Modified Wakao discloses the invention as discussed above in claim 1. Neither Wakao nor Ren discloses using sodium azide or zinc sulphate in the calibration liquid. In an analogous art, Kho discloses that sodium azide is known to be acutely cytotoxic at low millimolar concentrations, hence its use as a biological preservative (e.g., in antibodies) (Abstract).
It would have been obvious to one of skill in the art before the effective filing date to use sodium azide as preservative for the antibodies presented in the plurality of calibration liquids in Modified Wakao (Kho, Abstract).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICKEY HUANG whose telephone number is (571)272-7690. The examiner can normally be reached M-F 9:30-5:30 PM ET.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maris Kessel can be reached at 5712707698. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/M.H./Examiner, Art Unit 1758 /LYLE ALEXANDER/Supervisory Patent Examiner, Art Unit 1797
