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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 2/10/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Status
Claims 1-15 are pending.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-5 and 7-14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Huff et al (US 20180095067 A1; hereinafter “Huff”; already of record on IDS filed 2/10/2025).
Regarding claim 1, Huff teaches a method for loading microparticles into microwells (Huff; Abstract), the method comprising:
introducing a substrate solution into a detection component (Huff; para [324]; integrated digital microfluidic and analyte detection device 100 with a liquid droplet being moved in the gap 170), the detection component having a microwell array comprising a plurality of microwells, the substrate solution filling the microwells of the microwell array (Huff; para [324]; integrated digital microfluidic and analyte detection device 101 with a droplet 180 being moved in the gap 170 from the first portion 115 to the second portion 130 that includes the array of wells 160);
moving a plurality of solid supports into the detection component, the plurality of solid supports including a plurality of microparticles containing an analyte of interest (Huff; para [475]; a sample droplet containing the target analyte of interest may be merged with a droplet containing magnetic beads on which a first specific binding partner that specifically binds to the target analyte of interest present in the sample is attached and analyte labeled with a detectable label);
seeding, using a magnetic field, the plurality of microparticles into microwells of the microwell array (Huff; para [312]; droplet-based microfluidics refer to generating and actuating (such as moving, merging, splitting, etc.) liquid droplets via active or passive forces. Examples of active forces include, but are not limited to, electric field);
introducing an inert liquid into the detection component to form a number of sealed microwells, each sealed microwell containing an amount of substrate solution and a single microparticle sealed in the sealed microwell by the inert liquid (Huff; para [417]; the microfluidics device and/or the microfluidics module may include an inert fluid that is immiscible with the sample droplet and the reagent droplets…The inert fluid may facilitate formation of the fluidic droplets as well as increase stability of the shape of the fluid droplets and may further be useful for keeping the different droplets spatially separated from one another).
Regarding claim 2, Huff teaches the method of claim 1, wherein the substrate solution includes a phosphate-based material (Huff; para [492]; any suitable blocking reagent known to those of ordinary skill in the art may be used. For example phosphate buffered saline) and a wash buffer (Huff; para [173]; the solid support may be contacted with a wash buffer to remove any molecules non-specifically bound to the solid support).
Regarding claim 3, Huff teaches the method of claim 1, wherein the substrate solution is configured to activate a fluorescent signal from the microparticles with the analyte of interest bound thereto (Huff; para [174]; the complex of the first binding member and the analyte may be contacted with a second binding member, thereby leading to the formation of a sandwich complex in which the analyte is bound by the two binding members…the second binding member may include a detectable label comprising one or more signal-producing substances, such as fluorescent compounds). The Examiner notes that the addition of the second binding member activates the analyte for detection.
Regarding claim 4, Huff teaches the method of claim 1, wherein introducing the substrate solution includes flooding an area above the microwell array with the substrate solution (Huff; Fig. 4A, 4B).
Regarding claim 5, Huff teaches the method of claim 1, wherein a surface of the microwell array is hydrophilic (Huff; para [303]; prior to or after fabrication of the array of wells in the first layer, a hydrophilic layer may be disposed over the first layer in the second portion of the first substrate to provide an array of wells that have a hydrophilic surface).
Regarding claim 7, Huff teaches the method of claim 1, wherein each microwell is dimensioned to hold a single microparticle (Huff; para [332]; Each well may measure about 4.2 μm wide×3.2 μm deep (volume approximately 50 femtoliters), and may be capable of holding a single bead/particle).
Regarding claim 8, Huff teaches the method of claim 1, wherein moving the plurality of solid supports includes moving the plurality of solid supports by a magnetic force (Huff; para [134]; a first liquid droplet containing an analyte of interest, providing a second liquid droplet containing at least one solid support (such as, for example, a magnetic solid support (such as a bead)) which contains a specific binding member that binds to the analyte of interest, using energy to exert a force to manipulate the first liquid droplet).
Regarding claim 9, Huff teaches the method of claim 1, wherein seeding the microparticles includes introducing most or all of the microparticles into the microwells and removing remaining microparticles from a surface of the microwell array with the magnetic field (Huff; Fig. 16, 17; para [136]; such removing can involve generating an electric actuation force (such as that described previously herein) with a series or plurality of electrodes to move a fluid droplet (such as a polarizable fluid droplet) to the array of wells to move at least a portion of the mixture to a distance (the length of which is not critical) from the array of well).
Regarding claim 10, Huff teaches the method of claim 1, wherein after seeding, excess solid supports remain on a top surface of the microwell array, and wherein introducing the inert liquid into the detection component removes the excess solid supports from the top surface of the microwell array ((Huff; Fig. 16, 17; para [378]; a method in which the digital microfluidics electrodes (e.g. electrode 145) position the droplet 180 containing particles/beads or analyte molecules 190 over the array of wells 160. After a period of time sufficient for deposition of particles/beads/analyte molecules into the wells, the droplet is displaced by a droplet of immiscible liquid 195 (or an immiscible liquid as explained herein). The droplet of immiscible liquid functions to move droplet 180 with any bead/particles/analyte molecules not deposited into the wells away from the wells and to cover the wells).
Regarding claim 11, Huff teaches the method of claim 1, wherein the inert liquid comprises oil (Huff; para [417]; the inert fluid may be a heavy fluid that is denser than water, such as oil that is immiscible with the fluidic droplets being generated and processed in the microfluidics module).
Regarding claim 12, Huff teaches the method of claim 1, wherein introducing the inert liquid into the detection component includes pulling the inert liquid with a negative pressure (Huff; para [415]; The movement of fluidic droplet in the microfluidics and nanopore devices, modules, and the integrated devices may be carried out via any suitable means. The means for moving a fluidic droplet in different devices/modules and channels, if applicable, may be same or different. For example, fluidic droplets may be moved in the microfluidics device or module using fluidic manipulation force, such as pressure gradients (positive or negative)).
Regarding claim 12, Huff teaches the method of claim 1, further comprising obtaining images of the sealed microwells (Huff; para [599]; A CCD camera images the array to determine the number of positive and negative microparticles)
Regarding claim 14, Huff teaches the method of claim 1, further comprising single-molecule counting of the analyte of interest (Huff; para [133]; The method may involve single molecule counting).
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 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 6 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Huff.
Regarding claim 6, Huff teaches the method of claim 1, wherein the plurality of solid supports further includes assisting microparticles to assist with microparticle transportation (Huff; para [141]; the first liquid droplet (which contains the analyte of interest) with the second liquid (containing the at least one solid support) to create a mixture (namely, an analyte/detectable label-specific binding member complex) moving all or at least a portion of the mixture to an array of wells… bead may be a particle, e.g., a microparticle).
Huff does not teach the assisting microparticles having a size larger than the microwells.
However, Huff teaches in some embodiments, the microparticle may be between about 0.1 nm and about 10 microns, between about 50 nm and about 5 microns, between about 100 nm and about 1 micron, between about 0.1 nm and about 700 nm, between about 500 nm and about 10 microns, between about 500 nm and about 5 microns, between about 500 nm and about 3 microns, between about 100 nm and 700 nm, or between about 500 nm and 700 nm (Huff; para [167]) and a well of different sizes two shim designs were used to print two different well sizes (21) 4.2 μm wide×3.0 μm deep with a pitch of 8.0 μm; 4.5 μm×3.2 μm with a pitch of 8.0 μm (Huff; para [590]). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, to determine, through routine experimentation, the optimum size of the microparticles to be larger than the microwell which would allow prevent overcrowding of the wells because the wells are sized for a single molecule (MPEP § 2144.05 (II)).
Regarding claim 15, Huff teaches a method for loading microparticles into microwells, the method comprising:
introducing a substrate solution into a detection component, the detection component having a microwell array comprising a plurality of microwells (Huff; para [324]; integrated digital microfluidic and analyte detection device 100 with a liquid droplet being moved in the gap 170), the substrate solution filling the microwells of the microwell array (Huff; para [324]; integrated digital microfluidic and analyte detection device 101 with a droplet 180 being moved in the gap 170 from the first portion 115 to the second portion 130 that includes the array of wells 160);
moving a plurality of solid supports into the detection component, the plurality of solid supports including a plurality of microparticles containing an analyte of interest (Huff; para [327]; a liquid droplet 180 containing beads or particles 190 that has been moved to the second portion of the integrated device of FIG. 3A and is positioned over the array of wells 160), the plurality of solid supports further includes assisting microparticles to assist with microparticle transportation (Huff; para [141]; the first liquid droplet (which contains the analyte of interest) with the second liquid (containing the at least one solid support) to create a mixture (namely, an analyte/detectable label-specific binding member complex) moving all or at least a portion of the mixture to an array of wells… bead may be a particle, e.g., a microparticle);
seeding, using a magnetic field, the plurality of microparticles into microwells of the microwell array (Huff; para [312]; droplet-based microfluidics refer to generating and actuating (such as moving, merging, splitting, etc.) liquid droplets via active or passive forces. Examples of active forces include, but are not limited to, electric field);
introducing an inert liquid into the detection component to form a number of sealed microwells, each sealed microwell containing an amount of substrate solution and a single microparticle sealed in the sealed microwell by the inert liquid (Huff; para [417]; the microfluidics device and/or the microfluidics module may include an inert fluid that is immiscible with the sample droplet and the reagent droplets…The inert fluid may facilitate formation of the fluidic droplets as well as increase stability of the shape of the fluid droplets and may further be useful for keeping the different droplets spatially separated from one another).
Huff does not teach the assisting microparticles having a size larger than the microwells.
However, Huff teaches in some embodiments, the microparticle may be between about 0.1 nm and about 10 microns, between about 50 nm and about 5 microns, between about 100 nm and about 1 micron, between about 0.1 nm and about 700 nm, between about 500 nm and about 10 microns, between about 500 nm and about 5 microns, between about 500 nm and about 3 microns, between about 100 nm and 700 nm, or between about 500 nm and 700 nm (Huff; para [167]) and a well of different sizes two shim designs were used to print two different well sizes (21) 4.2 μm wide×3.0 μm deep with a pitch of 8.0 μm; 4.5 μm×3.2 μm with a pitch of 8.0 μm (Huff; para [590]). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, to determine, through routine experimentation, the optimum size of the microparticles to be larger than the microwell which would allow prevent overcrowding of the wells because the wells are sized for a single molecule (MPEP § 2144.05 (II)).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Austin Q Le whose telephone number is (571)272-7556. The examiner can normally be reached Monday - Friday 9am - 5pm.
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/A.Q.L./Examiner, Art Unit 1796
/REBECCA M FRITCHMAN/Primary Examiner, Art Unit 1758
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