DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This action is in response to applicant’s “Remarks”, filed April 24, 2026. The amendments therein have been thoroughly reviewed and entered. Any previous objection/ rejection not repeated herein has been withdrawn. Claims 1-9 are pending for examination. Claims 10-14 are withdrawn from consideration. The amendment filed in response to the Office Action mailed November 24, 2025 has been entered. This action is made FINAL. The amended independent claim 1 adds or clarifies, inter alia, that each well has an opening to the first surface and no other surface opening; that the first surface of the substrate and the cover member form opposite surfaces of a first fluid flow path; that the first fluid flow path includes a first inlet and a first outlet and is not connected to another inlet or outlet through which fluid flows; and that 0.8 <= Da/Dab <
Claim Interpretation
The claims are given their broadest reasonable interpretation (BRI) consistent with the specification. No unrecited embodiment limitation is imported into the claims. In particular, claim 1 does not require any particular degree of bubble removal, air displacement, filling efficiency, assay performance, or biological result merely because such effects are discussed in the specification. The numerical relationship 0.8 <= Da/Dab < 1 is treated as the positively recited structural limitation.
Likewise, the terms "well," "well array," "flow path," "cover member," "inlet," and "outlet" are construed according to the words of the claims rather than restricted to preferred embodiments. The expressly recited requirement that a well have a first opening to the first surface and no other surface opening is, however, given patentable weight. No limitation of claims 1-9 is interpreted under 35 U.S.C. 112(f) on the present record because the claims recite structural elements rather than a means-plus-function or other nonce formulation invoking section 35 USC 112(f).
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claims 1-9 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
. Claim 1 first recites "a first surface of the substrate," but later refers
to "the first surface of the well array." The claim does not clearly define a separate "first surface" of the well array. It is therefore unclear whether the later phrase refers to the first surface of the substrate, to a separate surface associated with the array, or to
another structure. The uncertainty is carried into dependent claims 2-9.
Claim 2 recites "the diameter of the first well opening." Amended claim 1
does not require the first well opening itself to be circular and does not presently define this diameter by reference to an area equivalent circle. The metes and bounds of the diameter limitation therefore are uncertain for a non-circular opening.
Claim 7 recites “a ratio of the diameter of the circle to a depth of the
wells," but no antecedent "circle" is presently introduced in the parent claim. It is therefore unclear which circle supplies the recited diameter.
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.
Claims 1-9 are rejected under 35 U.S.C. 103 (a) as being unpatentable over Makino et al., (US 20170233790; hereinafter “Makino” in view Maher et al., (US 20150045252; hereinafter “Maher”-already of record).
Regarding claim 1, as best understood, Makino teaches an array device having a base/substrate 3/4 with a plurality of bottomed wells 6, a cover over the wells, and a gap between the base and cover that serves as a channel for liquid flow from an injection port to a discharge port. Makino discloses a base 3 including substrate 4 and microporous array layer 5, bottomed tubular wells 6 formed by through holes Sa together with surface 4a of substrate 4, cover 7, and the gap serving as the liquid channel (see Figs. 1-4 and see para [0059] et seq., including the passages describing 5 μm opening, bottomed wells 6, the cover, and the injection/discharge ports).
Makino does not expressly teach the claimed numerical relationship 0.8 <= Da/Dab < 1.
Maher discloses a fluidic device comprising, as shown in Figure 3, substrate 102, 100 having a well array that includes a plurality of regularly arranged wells 104 that have the same shape and are open to at least two surfaces of the substrate, where the diameters of the well openings and spacing between the wells appear to satisfy the ratio condition as recited in the formula. Maher teaches that loading efficiency is affected by the relationship between well/reaction-site diameter and pitch. Maher explains that reducing spacing between adjacent reaction sites relative to well diameter reduces residual liquid and increases loading efficiency, and specifically evaluates loading as a function of pitch for fixed-diameter sites. Maher further teaches close packed
arrangements and numerical combinations including a 75 μm characteristic diameter with pitch values below 125 μm and a 60 μm diameter with an 82 μm pitch (see para [0048] et seq. and Figs. 4-7 and 9).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the diameter and center-to-center spacing of Makino's regularly arranged wells in accordance with Maher because Maher expressly identifies well diameter and pitch/density as variables that control liquid-loading efficiency and residual liquid. A person of ordinary skill therefore would have had a reason to reduce pitch relative to well diameter in Makino while preserving the known array/cover/flow-path architecture. The modification would have involved routine adjustment of two known geometric parameters with a predictable effect on loading. A reasonable expectation of success is supplied by Maher's express modeling and examples showing the effect of decreased spacing at a given site diameter.
It would have been also obvious to have varied the well diameters and spacings between the wells within a wide range of values and proportions, including those recited, in order to optimize distribution of liquid reagents or solutions used for testing, depending on particular goals and to diversify the tests to be conducted, in view of the Maher’s considerations in para [0040], where Maher explains that the reaction site [i.e., well] density, associated with the ratio condition, may be optimized, for example, by ‘reducing ratio of the value of the spacing between adjacent well to the value of the well diameter’, to optimize the amount of solution so that ‘an initial solution or sample containing biological components of interest is located inside reaction sites 104’.
Claim 2, as best understood, requires a first well opening diameter from 1 μm to 50 μm. Makino teaches 5 μm diameter through holes forming the bottomed wells and also states that individual well dimensions may be appropriately determined. The 5 μm diameter is within the claimed range (see para [0066] et seq.). Similarly, Maher explains in [0046] that the diameters of wells 104 is ‘less than or equal to 20 micrometers, less than or equal to 10 micrometers, less than or equal to 1 micrometer, or less than or equal to 100 nanometers. The pitch between reaction sites [‘wells’-Ex.] may be less than 125 micrometers, for example, less than or equal to 100 micrometers, less than or equal to 30 micrometers, less than or equal to 10 micrometers, or less than or equal to 1 micrometer.’
Claim 3 requires the ratio of total well-opening area to the area of the well array to be 30%-90%. Maher teaches dense, close-packed arrays and specifically teaches increasing site density by decreasing pitch (see para [0041] et seq.) A 75 μm circular opening arranged at a 100 μm pitch in a close-packed hexagonal array produces an opening-area fraction of approximately 51%, from the open-area fraction calculation Area \%=Area of holes/Total area of repeating cell×100, which is within the claimed range. Maher therefore teaches or renders obvious the additional area-fraction limitation when its close-packed geometry is used in the modified Makino device.
Claim 4 requires each well to have a volume of 10 fL to 100 pL. Makino teaches a 5 μm diameter, 3 μm long microchamber of about 100 fl, and states that the capacity of each through hole may be appropriately determined and may be 10 pl or less. The expressly taught approximately 100 fl volume lies within the claimed range (see para [0066] et seq.).
Claim 5 requires a total volume of the wells of 0.2 to 2.0 µL. Maher teaches dividing an initial sample among very large numbers of reaction sites and expressly identifies both the number of reaction sites and the per-site volume as design parameters. Maher teaches at least ten thousand, at least one hundred thousand, at least one million, or at least ten million reaction sites, with individual reaction-site volumes on the order of nanoliters or less, including 100 pl or less, 10 pL or less, and 1 pL or less. Maher teaches examples in which individual reaction-site volume can be 30 pl or less and describes articles containing at least 12,000 or larger numbers of sites (see para [0047] et seq.) It would have been obvious to select the number of wells and individual well volume in the modified Makino array so that the aggregate capacity is 0.2-2.0 µL. The total well volume is the mathematical product of two parameters that Maher expressly teaches the artisan to select the number of sites and the volume of each site• in order to divide and retain an initial sample. For example, 12,000 sites at 30 pL correspond to 0.36 µl total capacity, within the claimed range. The prior art therefore presents a finite and predictable set of combinations of known site counts and known site volumes, and the skilled artisan would have had reason to select among those combinations according to desired sample capacity and partition count. Makino teaches the same two physical volumes that define the claimed ratio. The wells have selectable capacities, and the space between the microporous array layer and the cover forms the flow channel. Makino expressly teaches a 100 μm gap between the array layer and the cover and states that well capacity may be appropriately determined (see para [0125] et seq.) Maher teaches selecting site number, site volume, pitch and density to increase loading efficiency and reduce residual sample outside the reaction sites (see para [0041] et seq. and Figs. 4-7). It would have been obvious to optimize the aggregate well capacity relative to the overlying flow-path volume because both volumes directly determine how much introduced liquid resides in the wells versus remains in the channel. Maher expressly identifies that distribution sample captured by reaction sites versus residual liquid outside the sites as an optimization concern and teaches increasing the fraction captured in the sites by changing array geometry. Once the artisan has the known Makino well array and overlying flow channel, there are only a limited number of predictable ways to alter that volumetric distribution: increase/decrease well number or well volume, and/or increase/decrease the channel gap/plan area. Selecting a ratio in which wells account for 5%-40% of the flow-path volume would have been an obvious matter of routine optimization/obvious to try where the result sought is increased capture in the wells while retaining sufficient channel volume for reagent delivery. A person of ordinary skill would have had a reasonable expectation of success because changing these dimensions does not require a new operating principle. Makino already teaches functioning wells below a cover defined flow channel, and Maher teaches that changing the relative amount of liquid captured in the wells predictably changes loading efficiency. There does not appear to be any criticality for the particular 5%-40% interval.
Claim 7, as best understood, requires a ratio of the diameter of the recited circle to a depth of the wells of 3%-200%. Makino teaches 5 μm diameter through holes having a 3 μm length/depth in the microporous layer (see para [0010] et seq.) The corresponding diameter-to-depth ratio is 5/3 x 1000/4 = approximately 166.7%, within the claimed 3%-200% range.
Regarding claim 8 Makino teaches that the microporous array layer can be made from a hydrophobic resin and defines hydrophobicity as a water contact angle of 70 degrees or more, providing examples of approximately 85 degrees for cycloolefin polymer and approximately 110 degrees for CYTOP, see para [0073] et seq.
Claim 9 requires the surface of the cover member facing the well array to have a water contact angle of 70-180 degrees. Makino teaches hydrophobic materials and expressly defines hydrophobicity as a water contact angle of 70 degrees or more,
with disclosed examples of approximately 85 degrees and 110 degrees (see para [0072] et seq.) It would have been obvious to employ a hydrophobic material on the facing surface of the cover where hydrophobic surface behavior is desired in the liquid-contacting region, using the same known class of materials and contact-angle properties Makino expressly teaches for the array device. The selection would predictably provide the known wetting characteristic.
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.
Response to Arguments
Applicant's arguments filed April 24, 2026 have been fully considered but they are not persuasive. To the extent applicant relies on the requirement that each well have an opening to the first surface and no other surface opening, Makino's completed structure includes bottomed tubular wells 6. Although through holes Sa are formed in the microporous array layer during fabrication, those holes together with the underlying substrate surface form bottomed wells in the completed device. The rejection is based on the finished structure, not on an isolated fabrication layer.
To the extent applicant relies on the substrate surface and cover member forming opposite surfaces of the fluid flow path, Makino expressly teaches a cover positioned over the base with a gap therebetween serving as the channel through which liquid passes from the injection port toward the discharge port.
To the extent applicant relies on the claimed single inlet/single outlet relationship, Makino teaches an injection port communicating with the gap/channel and a discharge port positioned apart from the injection port and communicating with the same gap. The existence of wells communicating with the overlying path does not transform those well openings into additional "inlets" or "outlets" through which fluid flows into or out of the claimed flow path in the ordinary sense of those terms.
To the extent applicant relies on the 0.8 <= Da/Dab < 1 limitation, Maher expressly teaches that the ratio of well size to spacing/pitch is a parameter affecting liquid loading and residual liquid. The instant rejection therefore does not rely on hindsight selection of an unrelated dimension; it follows the prior art's express direction to adjust the same variables for the same general liquid-loading problem.
Pertinent Prior Art
The following prior art is hereby made of record. Although the prior art is relied upon, the examiner considers the listed prior art relevant to the applicant’s invention and may be relied upon in a future prior art rejection or as general background information related to applicant’s field of endeavor.
a. Makino et al., (US 20160333400; already of record) is cited as pertinent to the address the latest amendment in applicant’s corresponding EP 21864305 which recites claim 1 and a fluid comprising an aqueous medium containing a surfactant. Makino teach supplying a reagent to a plurality of wells, wherein the reagent may contain an adsorption inhibitor comprising a surfactant, including a nonionic surfactant such at Tween 20 or Trition X-100. Makino teach that the surfactant reduces surface tensions and facilitates introduction of the reagent into the wells.
b. Handique et al. (US 20190060902; already of record) is cited for applicant's consideration but is not applied above. Handique teach a substrate having an array of wells, an overlying fluid reservoir/path, a lid, flow parallel to the well-array surface, selectable well dimensions/volumes, and adjustment of lid-groove dimensions to provide specified liquid dead volumes, see Figs. 1-3 and 28A-33 (see the description of the fluid reservoir 160/fluid pathway 162 and grooves 165, and description of well dimension/volume selection. Handique is particularly relevant to the concept that array capacity and overlying fluid volume are engineering parameters
Conclusion
No claims are allowed.
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 nonprovisional extension fee (37 CFR 1.17(a)) 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 P. Kathryn Wright whose telephone number is (571)272-2374. The examiner can normally be reached between 9:30am-7pm EST.
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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.
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/P. Kathryn Wright/Primary Examiner, Art Unit 1798
