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 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.
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);
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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.
In an analogous art, Ren discloses a hydrophobic, single-sided tape used to seal the inlet and outlet of acrylic microfluidic chip (Figure 4a). It would have been obvious to one of ordinary skilled in the art to have incorporate a tape layer such as the one taught by Ren to seal off the opening of the microfluidic channels of Wakao. Doing so comes with the benefits of preventing leaks and maintaining enclosed fluid paths and preventing contamination.
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 know 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.
In an analogous art, Ren discloses applying hydrophobic, single-sided tape used to seal the inlet and outlet of acrylic microfluidic chip (Figure 5). It would have been obvious to one of ordinary skilled in the art to have incorporate a tape layer such as the one taught by Ren to seal off the opening of the microfluidic channels of Wakao. Doing so comes with the benefits of preventing leaks and maintaining enclosed fluid paths and preventing contamination.
Claim 4 is rejected under 35 U.S.C. 103 as being obvious over Wakao in view of Ren 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).
Response to Arguments
Applicant's arguments filed on 11/14/2025 have been fully considered but they are not persuasive.
The remark is directed on the grounds that Ren’s disclosure involves sealing microfluidic channels by applying a sealing tape to the surface of the substrate where the channels are formed, yet the sealing tape is not applied on a surface of the substrate opposite to the surface where the channels are formed and thus through-holes (inlets of the microfluidic channels) connecting to the microfluidic channels remain opens, and therefore, one of ordinary skill in the art would not have applied teaching of Ren to cure the deficiency of Wakao. Examiner respectfully disagrees.
The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
First, referring to Figure 1A of Wakao, Wakao implicitly discloses while the channel partitions are facing the first substrate/glass slide, the inlets and outlets (or the openings) of the channels remain facing in the direction opposite of the glass slides. This is implicitly support by Wakao’s statement of need of using vacuuming through the inlet either to remove air or excess liquids (Air was removed from the microdevice by applying adequate vacuum; then the sample was dropped into the inlet and introduced into the microchannel by suction from the outlet.20 From there, the sample filled the microchambers, and the excess sample in the microchannel was removed by air injection from the inlet. Fabrication of the PDMS-glass microdevice, paragraph 2), which can only be achieved by having the opening facing opposite of the glass slide. However, the openings are still left opening to the atmospheric environment.
Examiner believes this deficiency can be partially (if not fully alleviated) by the addition of another layer to seal these openings with teaching such as Ren, which, at the minimum, discloses sealing tape layer that seals an opening/inlet/outlet along with the channel cavity. Furthermore, both Examiner and Ren (at least at the introduction) surmises the advantage of using the acrylic layer for sealing openings is to prevent contamination (Furthermore, acrylic, also referred to as poly(methyl methacrylate) (PMMA), is non-porous and hence can prevent adsorption or absorption related contaminations. Introduction, paragraph 2). As the advantage and the technical direction (an acrylic adhesive layer being applied manually onto cavities of a microfluidic layer) were given, Examiner believes it would have been obvious to one of ordinary skill in the art to utilize a third adhesive layer to seal the inlet/opening of the device of Wakao in order to prevent further foreign objects from entering the opening from surrounding atmosphere. For the reason above, the rejection is maintained.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
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/M.H./Examiner, Art Unit 1758 /LYLE ALEXANDER/Supervisory Patent Examiner, Art Unit 1797