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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 11/06/2025 has been entered.
Remarks
This office action fully acknowledges Applicant’s remarks and amendments filed on 06 November 2025.
Claims 1-15 and 23-29 are pending.
Claims 16-22 are cancelled.
Claims 12-15 are withdrawn from consideration.
Claim 1 is amended.
Claim Rejections - 35 USC § 112
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 1-11 and 23-29 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites “a compressible pad disposed on the top surface, the compressible pad configured to provide more thorough and consistent heat transfer to the first amplification chamber and the second amplification chamber from a plurality of contact heat sources in contact with a bottom surface of the microfluidic cartridge”. Therein, it is unclear how the compressible pad is “configured to provide more thorough and consistent heat transfer...from a plurality of contact heat sources” given that said compressible pad is positioned away from the cartridge/heat source interface, thereby appearing incapable of providing the claimed heat transfer to the cartridge from the heat sources, given that in the claimed arrangement, the cartridge itself appears to be transferring heat to the compressible film as in intervening element between the heat sources and the compressible film and not vice versa. Appropriate clarification is required. Claims 2-11 and 23-29 are further rejected through their dependence on Claim 1.
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 1-5, 8-11, and 23-29 are rejected under 35 U.S.C. 103 as being unpatentable over Handique (US 2014/0323357 A1), referred to hereinafter as “Handique”, in view of Schnell et al. (US PAT 7,256,035 B1), hereinafter “Schnell”, and Breidenthal et al. (US 2009/0142745 A1), hereinafter “Breidenthal”.
Regarding Claim 1, Handique teaches a microfluidic cartridge comprising a first side and an opposing, second side, comprising:
a first amplification chamber a second amplification chamber a first inlet configured to accept a first liquid transfer member inserted into a top surface (Fig. 2A – see inlets 202.), the first inlet disposed on the first side, in fluid communication with the first amplification chamber, a second inlet configured to accept a second liquid transfer member inserted into the top surface (Fig. 2A – see inlets 202.), the second inlet in fluid communication with the second amplification chamber ([0009]: “In particular, the present technology provides for a microfluidic cartridge, comprising: a first PCR reaction chamber; a second PCR reaction chamber; a first inlet, in fluid communication with the first PCR reaction chamber; a second inlet, in fluid communication with the second PCR reaction chamber…”); and
a compressible pad 420, the compressible pad 420 configured to provide more thorough and consistent heat transfer to the first amplification chamber and the second amplification chamber from a plurality of contact heat sources in contact with a bottom surface of the microfluidic cartridge, the bottom surface opposite the top surface (Figs. 4A and 4C, and [0074]: “The layer 420 can be compressible and have a higher thermal conductivity than common plastics, thereby serving to transfer heat across the laminate more efficiently.” – Fig. 8 and [0019]: “…at least one heat source thermally coupled to the cartridge and configured to apply heat and cooling cycles that carry out PCR on one or more microdroplets of polynucleotide-containing sample in the cartridge…” – Fig. 14 further shows the heaters 909/911 on the bottom surface of the cartridge, adjacent to the compressible layer 907.),
a first opening aligned with the first amplification chamber and a second opening aligned with the second amplification chamber, the first opening and the second opening configured to allow light to be transmitted through the top surface of the microfluidic cartridge to and from the first amplification chamber and the second amplification chamber, respectively ([Fig. 2A and [0064]: “Above each PCR reactor 210 is a window 212 that permits detection…”), as in Claim 1.
Further regarding Claim 1, Handique does not specifically teach the cartridge discussed above wherein the compressible pad is disposed on the top surface, as in Claim 1.
However, Schnell teaches a respective PCR cartridge (col. 3, line 62) comprising a cartridge 1 clamped between two opposing heating blocks 40’ (Fig. 7 and col. 9, line 30), wherein said cartridge comprises opposing walls used for heat transfer to ensure heat is conducted into the cartridge (col. 2, line 62: “heat conducting walls of the cartridge” – see also col. 1, line 66 “The cartridge of the present invention has the shape of a thin plate. The two opposing larger walls are used for heat transfer and one or more walls substantially vertical thereto are used for transmitting light into the cartridge and for transmitting light to be detected out of the cartridge. This cartridge design ensures that the optical path and the path for heat exchange are spatially separated so that detection and heat transfer do not compete for space.” – See also Schnell Chaim 3.). Therein, this arrangement provides for more rapid and even heating of the cartridge (col. 9, line 33: “intensive thermal contact between the cartridge and the heating unit”), as would be understood by one skilled in the art from established scientific principles (more heaters leads to faster heating, heaters on both sides leads to even heating/reduced heat gradient across the thickness), thereby improving consistency between analytical runs and between multiplexed chambers of the same cartridge.
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the cartridge of Handique to provide an additional heating block and additional compressible layer (heat conducting wall) to the top surface, such as suggested by Schnell, so as to provide for more rapid and even heating of the cartridge, thereby improving consistency between analytical runs and between multiplexed chambers of the same cartridge.
Further regarding Claim 1, Handique does not specifically discuss the first and second openings as included in the compressible pad, as in Claim 1.
However, Breidenthal teaches a respective cartridge comprising thermally conductive foil layers for conducting heat into the cartridge, wherein said conductive foil layers comprise cut-out window openings so as to provide optical detection windows ([0254]). Further, Handique teaches the window 212 of the upper layer 428 (Figs. 2B and 4A.) for permitting optical interrogation of the PCR chambers ([0064]: “Above each PCR reactor 210 is a window 212 that permits detection of fluorescence from a fluorescent substance in PCR reactor 210 when a detector is situated above window 212. It is to be understood that other configurations of windows are possible including, but not limited to, a single window that straddles each PCR reactor across the width of cartridge 200.”).
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the cartridge of Handique to provide individual (first/second) openings, such as suggested by Breidenthal, to the amplification chambers of Handique having a singular common opening, as a mere obvious alternative arrangement known in the art as shown through Breidenthal and alluded to through Handique achieving the identical result of providing fewer materials between the optical interrogator and the sample contained in the PCR chambers so as to reduce interference/interaction of the light with added material intervening with the amplified sample. Further, one skilled in the art would find it obvious to carry this same principle (providing openings/windows for optical analysis) when providing the additional thermally conductive layer suggested by Schnell so as to maintain the optical window, further given that Schnell and Breidenthal commensurately teach thermally conductive layers on both sides of the cartridge and optical interrogation of said cartridge.
Regarding Claim 2, the prior art meets the limitations of Claim 1 as discussed above. Further, Handique teaches the PCR cartridge discussed above wherein the first amplification chamber and the second amplification chamber have a volume of about 25 μL ([0052]: “…volumes of sample, and/or reagent, and/or amplified polynucleotide are from about 0.1 μL to about 999 μL, such as from 1-100 μL, or from 2-25 μL.”), as in Claim 2.
Regarding Claim 3, the prior art meets the limitations of Claim 1 as discussed above. Further, Handique teaches the PCR cartridge discussed above wherein the first amplification chamber and the second amplification chamber have a width dimension of about 3.5 mm, a depth dimension of about 0.83 mm, and a length dimension of about 10 mm ([0193]: “This 24-lane cartridge has two rows of 12 sample lanes. Each lane has: a liquid inlet port, that interfaces with a disposable pipette; a 4 microliter PCR reaction chamber (1.5 mm wide, 300 microns deep and approximately 10 mm long)…”), as in Claim 3.
Further regarding Claim 3, Examiner further notes that while the dimensions disclosed by Handique are not necessarily identical to the claimed dimensions, the dimensions are claimed as being “about” the recited value. As such, Examiner asserts that the dimensions taught by Handique are “about” the same as the claimed dimensions, as both sets of dimensions are on the same order of millimeters wide/long and a fraction of a millimeter deep.
Further note that mere change in size (where the only difference between the prior art and the claims is a recitation of relative dimensions of the claimed device and a device having the claimed relative dimensions would not perform differently than the prior art device) absent evidence to criticality, non-obviousness, or unexpected results associated with the claimed shape is an obvious matter of design choice – see MPEP 2144.04(IV)(A). As such, the claimed dimensions of PCR amplification chambers are merely an obvious matter of design choice as the mechanism of PCR reactions occurring therein proceed the same no matter the dimensions of the chamber, and wherein Handique further discusses the thinness of the cartridge being related to rapid temperature cycling ([0121]) as similarly contemplated by the instant cartridge.
Regarding Claim 4, the prior art meets the limitations of Claim 1 as discussed above. Further, Handique teaches the PCR cartridge discussed above wherein the microfluidic cartridge comprises a label 2632 above the compressible pad ([0197]: “FIG. 26 shows a representative sample kit 2610 that includes a microfluidic cartridge 2612 with a barcode label 2632…”), as in Claim 4.
Regarding Claim 5, the prior art meets the limitations of Claim 1 as discussed above. Further, Handique teaches the PCR cartridge discussed above wherein the first amplification chamber, the second amplification chamber, the first inlet, and the second inlet are formed in a rigid substrate layer 424 (Fig. 4A and [0070]: “Additionally, the material from which this substrate is formed is rigid or non-deformable…Rigidity is advantageous because it facilitates effective and uniform contact with a heat unit as further described herein.),
and wherein the second side of the microfluidic cartridge comprises a flexible laminate layer below the first amplification chamber and the second amplification chamber (Fig. 4A and [0074]: “The cartridge can further include a heat sealable laminate layer 422 (typically between about 100 and about 125 microns thick) attached to the bottom surface of the microfluidic substrate 424 using, for example, heat bonding.”), as in Claim 5.
Regarding Claim 8, the prior art meets the limitations of Claim 1 as discussed above. Further, Handique teaches the PCR cartridge discussed above wherein the compressible pad improves pressure distribution from a component of a diagnostic testing apparatus (While Handique does not explicitly state this effect, para. [0075] discusses application of pressure to the cartridge to the heater for “achieving better thermal contact between the heater and the heat-receiveable parts of the cartridge”. – As the compressible pad 420 is deformable, this compression will deform the pad 420 such that it contacts all areas of the cartridge and the heater, thereby eliminating any gaps or inconsistencies in pressure that would result in non-uniform heating.), as in Claim 8.
Regarding Claim 9, the prior art meets the limitations of Claim 1 as discussed above. Further, Handique teaches the PCR cartridge discussed above wherein application of pressure to the compressible pad is configured to increase uniformity of the application of heat from the plurality of contact heat sources to the first amplification chamber and the second amplification chamber ([0074]: “The layer 420 can be compressible and have a higher thermal conductivity than common plastics, thereby serving to transfer heat across the laminate more efficiently.”), as in Claim 9.
Regarding Claim 10, the prior art meets the limitations of Claim 1 as discussed above. Further, Handique teaches the PCR cartridge discussed above wherein the compressible pad increases uniformity of the application of heat to the first amplification chamber and the second amplification chamber ([0074]: “The layer 420 can be compressible and have a higher thermal conductivity than common plastics, thereby serving to transfer heat across the laminate more efficiently.” – As the laminate covers all of the chambers, it thereby increases uniformity of the application of heat to the first amplification chamber and the second amplification chamber.), as in Claim 10.
Regarding Claim 11, the prior art meets the limitations of Claim 1 as discussed above. Further, Handique teaches the PCR cartridge discussed above wherein the compressible pad enhances PCR amplification which relies on rapid temperature cycling ([0074]: “The layer 420 can be compressible and have a higher thermal conductivity than common plastics, thereby serving to transfer heat across the laminate more efficiently.” – As the layer 420 allows heat to be more efficiently transferred to the cartridge, it enhances PCR amplification by quickly heating and cooling the sample. – See further para. [0121] which discusses rapid heating and cooling.), as in Claim 11.
Regarding Claim 23, the prior art meets the limitations of Claim 1 as discussed above. Further, Handique teaches the PCR cartridge discussed above wherein the microfluidic cartridge is configured for use with an apparatus comprising a bay configured to receive the microfluidic cartridge, wherein the bay comprises the plurality of contact heat sources ([0160]: “In some embodiments, an apparatus includes: a receiving bay configured to selectively receive a microfluidic cartridge as described herein; at least one heat source thermally coupled to the receiving bay…”), as in Claim 23.
Regarding Claim 24, the prior art meets the limitations of Claim 1 as discussed above. Further, Handique teaches the PCR cartridge discussed above wherein the microfluidic cartridge is configured for use with a detector which is disposed above the microfluidic cartridge during detection ([0064]: “Above each PCR reactor 210 is a window 212 that permits detection of fluorescence from a fluorescent substance in PCR reactor 210 when a detector is situated above window 212.”), as in Claim 24.
Regarding Claim 25, the prior art meets the limitations of Claim 1 as discussed above. Further, Handique teaches the PCR cartridge discussed above wherein the compressible pad is configured to be compressed by a detector which is disposed above the microfluidic cartridge during detection ([0171]: “…various depictions show a heater substrate disposed underneath a microfluidic substrate, and a detector disposed on top of it…” – As para. [0169] discusses the apparatus compressing the cartridge in the receiving bay, the detector disposed on top thereby compresses the cartridge.), as in Claim 25.
Regarding Claim 26, the prior art meets the limitations of Claim 1 as discussed above. Further, Handique teaches the PCR cartridge discussed above wherein the microfluidic cartridge comprises a first layer, a second layer, and a third layer that together define a plurality of microfluidic networks (Fig. 4A shows layers of the device, comprising at least three layers as claimed.), as in Claim 26.
Regarding Claim 27, the prior art meets the limitations of Claim 1 as discussed above. Further, Handique teaches the PCR cartridge discussed above wherein the compressible pad is positioned below a label ([0197]: “FIG. 26 shows a representative sample kit 2610 that includes a microfluidic cartridge 2612 with a barcode label 2632…”), as in Claim 27.
Regarding Claim 28, the prior art meets the limitations of Claim 1 as discussed above. Further, Handique teaches the PCR cartridge discussed above wherein the compressible pad comprises a pressure sensitive adhesive ([0074]: “The cartridge can further include a thermal interface material layer 420 (typically about 125 microns thick), attached to the bottom of the heat sealable laminate layer using, for example, pressure sensitive adhesive.”), as in Claim 28.
Regarding Claim 29, the prior art meets the limitations of Claim 1 as discussed above. Further, Handique does not specifically teach the PCR cartridge discussed above wherein the compressible pad comprises a heat sealable layer, as in Claim 29.
However, Handique teaches a separate compressible pad 420 and a heat sealable layer 424 ([0074]). Herein, merely making integral as one piece what exists in the prior art as separate pieces absent any criticality or unexpected result is an obvious matter of design choice – see MPEP 2144.04 (V)(B).
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the device of Handique such that the compressible pad is also a heat sealable layer, so as to reduce the manufacturing complexity of the device, for example; and would have a reasonable expectation of success therein.
Claims 6-7 are rejected under 35 U.S.C. 103 as being unpatentable over Handique in view of Schnell and Breidenthal, as applied to Claims 1-5, 8-11, and 23-29 above, and in further view of Goodman et al. (US 2004/0137604 A1), referred to hereinafter as “Goodman”.
Regarding Claims 6-7, the prior art meets the limitations of Claim 1 as discussed above. Further, Handique/Schnell/Breidenthal does not specifically teach the PCR cartridge discussed above wherein the compressible pad comprises a material with a Compression Force Deflection less than 30 psi nor less than 20 psi to deflect the material 25% of its original height, as in Claims 6-7.
However, the instant specification teaches the material comprising the compressible pad as PORON foam in certain embodiments ([0157]).
Further, Goodman teaches a respective cartridge comprising an insert 313 for controlling and localizing thermal delivery to the cartridge, wherein said insert 313 is formed from a compressible PORON layer ([0049]), and wherein the cartridge has application with PCR ([0106]). As discussed in MPEP 2112.01, "Products of identical chemical composition cannot have mutually exclusive properties." Therefore, the PORON foam of Goodman must also exhibit a Compression Force Deflection less than 30 psi and less than 20 psi as it is the same material used by the instant cartridge of Applicant’s disclosure for the compressible pad (par.[0145] of Applicant’s pre-grant publication US 2022/0212190).
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the cartridge of Handique/Schnell/Breidenthal to fabricate the thermal interface material layer 420 from PORON foam, which exhibits a Compression Force Deflection less than 30 psi and less than 20 psi as claimed, so as to provide a particular compressible material to that of Handique’s and that provides the benefit of achieving more localized thermal delivery to the cartridge, thereby accelerating PCR occurring therein and increasing throughput; and would have a reasonable expectation of success therein.
Response to Arguments
Rejection of Claims under 35 USC 103
Applicant’s arguments are on the grounds that Handique does not teach the compressible pad on the top surface opposite a bottom surface in contact with the heating elements, as in the amendments to Claim 1.
Applicant’s arguments are not persuasive because the additional reference of Schnell, added herein as necessitated through Applicant’s amendments further specifying the positions of the top and bottom surfaces, teaches conductive heating layers/pads/walls on both sides of the cartridge so as to provide rapid and even heating through a dual heating block assembly heating from both the top and bottom sides. Therein, one skilled in the art would find it obvious to provide the dual-heater assembly and an additional compressible thermal pad to the top surface of Handique so as to achieve the benefits of rapid and even thermal cycle heating, as is emphasized by the prior art as important considerations when performing PCR.
Applicant’s arguments are further on the grounds Handique does not teach openings in the compressible pad above each amplification chamber, as in the amendments to Claim 1 specifying the windows as openings.
Applicant’s arguments are not persuasive because the additional reference of Battrell, added herein as necessitated through Applicant’s amendments further specifying the windows as being openings, teaches discrete, individual openings in a thermally conductive foil layer allowing for optical interrogation of sample in the chambers below the openings. Further, Handique teaches an opening in a layer above all of the reaction chambers so as to remove unnecessary material between the optical source/detector and the sample, thereby removing potential interference. As discussed in the body of the action, one skilled in the art would find it obvious to provide this top layer with a plurality of openings, as opposed to a single opening, as a mere obvious alternative achieving the identical result of removing/avoiding optical interference and providing discrete optical analysis regions and would have a reasonable expectation of success in the device of Handique. Further, as provided through Schnell, the openings are provided to an additional compressible layer of the top surface of Handique so as to maintain the principles of Handique and Battrell of reducing optical interference, while maintaining to provide the additional thermal interface as suggested by Schnell.
Thus, Examiner respectfully sets forth the rejection of Claim 1 and its dependents under 35 USC 103 as unpatentable over Handique in view of Schnell and Breidenthal, as discussed above in the body of the action.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BENJAMIN JOSEPH KASS whose telephone number is (703)756-5501. The examiner can normally be reached Monday - Friday from 9:00 A.M. to 5:00 P.M. EST. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jill Warden, can be reached at telephone number (703)756-5501. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/B.J.K./Examiner, Art Unit 1798
/NEIL N TURK/Primary Examiner, Art Unit 1798