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 .
Remarks
This office action fully acknowledges Applicant’s remarks and amendments filed on 09 June 2026.
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Claims 12-15 are withdrawn from consideration.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 § 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 enable a more uniform contact between the microfluidic cartridge and a plurality of contact heat sources in contact with a bottom surface of the microfluidic cartridge, thus providing 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-receivable 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 112
Applicant’s amendment to Claim 1 sufficiently overcomes the rejection of Claim 1 as indefinite under 35 USC 112(b) as set forth by the previous office action. As such, the rejection of Claim 1 under 35 USC 112(b) is withdrawn herein.
Rejection of Claims under 35 USC 103
Applicant argues on the alleged grounds that the combination of Handique, Schnell, and Breidenthal fails to teach or suggest “the compressible pad configured to enable a more uniform contact between the microfluidic cartridge and a plurality of contact heat sources in contact with a bottom surface of the microfluidic cartridge, thus providing more thorough and consistent heat transfer” as in the amendment to Claim 1.
Applicant’s arguments are not persuasive because Handique teaches the pertinent core structure and the recited functional relationship of a compressible pad 420 for improved heat transfer ([0074]) wherein one of ordinary skill in the art would expect such compressibility of the pad to result in more uniform contact as a compressible member would be known to change shape as it is compressed, exerting a substantially even force as it is compressed, thereby eliminating gaps between the heating block and the cartridge which would impede thermal flow. This is further supported in para. [0075] where Handique discusses increased pressure of the clamping mechanism resulting in better thermal contact, thereby further providing that uneven/non-uniform contact hinders thermal flow and indicating the compressibility of the pad 420 as a key means for bridging the gap(s) between the heating element and the cartridge. Therein, a skilled artisan would infer that the compressible pad of Handique provides a more uniform contact between the microfluidic cartridge and a plurality of contact heat sources in contact with a bottom surface of the microfluidic cartridge, thus providing more thorough and consistent heat transfer, commensurately as claimed. Schnell provides the top-side compressible pad, and Breidenthal provides the optical openings in the pad. Thus, each and every limitation of Claim 1 is accounted for by the combination of Handique, Schnell, and Breidenthal.
Applicant further argues on the alleged grounds that Schnell is silent regarding an “additional compressible layer” on the top surface, as required by Claim 1, and points out the cartridge body shown in Schnell Fig. 1 a is formed from a solid propylene block and is not compressible.
Applicant’s arguments are not persuasive because they address Schnell in isolation. The rejection does not require the cartridge body of Schnell or its heat-conducting well to be compressible or covered by a compressible element. Schnell is relied on for its teaching of compressing and heating a cartridge from opposing sides using two plates, the opposing thermal elements of which establishing intensive thermal coupling for rapid heating and cooling from both sides rather than just one for more even heating. To the extent that Applicant has interpreted Schnell as providing the additional pad, the record is clarified: Schnell is merely relied upon for dual-sided heating, wherein one of ordinary skill in the art implementing this arrangement into Handique would find it obvious to provide the cartridge of Handique with an additional thermal layer so as to commensurately thermally couple the additional heating block in the same manner and achieving the same benefits as the lone thermal pad in Handique. Thus, the compressible pads are provided by Handique, and the top-side arrangement is supplied by Schnell, and the skilled artisan would have found it obvious to combine them for improved thermal control over the cartridge.
Applicant further argues on the alleged grounds that Examiner failed to cite support for statements concerning reasoned benefits of combining/modifying the prior art to yield the apparatus of Claim 1, such as improved heating speed and evenness, allegedly depriving Applicant of an opportunity to respond completely and with particularity.
Applicant’s arguments are not persuasive because a citation of support is not a prerequisite preventing or allowing Applicant to respond to statements made in an office action. Further, the reasoning to modify Handique in view of Schnell and Breidenthal provided by the prior office action rests on affirmative evidence in the cited references and the reasoned inferences which a person of ordinary skill in the art would draw from such evidence. Handique discusses the need for effective and uniform contact ([0070]), teaches a compressible thermally-conductive layer for enhancing thermal coupling to the cartridge ([0074]), that higher contact pressure provides better thermal coupling ([0075]), and that applied force ensures consistent thermal contact ([0174]). Schnell merely suggests heisting the cartridge from both sides (col. 3, col. 9, Figs. 6-7), wherein one of ordinary skill in the art would easily reason that such an arrangement would result in faster, more consistent heating, as more heaters allows a greater heat capacity to be delivered within a period of time, and that heating symmetrically from both sides causes the sample to reach a uniform temperature rather than if the cartridge is heated asymmetrically from only one side. Further, Breidenthal is merely relied on for providing an optical window in the pad so as to reduce interference with a light beam ([0064], Figs. 2B and 4A), wherein the skilled artisan would easily reason that fewer obstacles in a light path will result in less interference and give a more accurate and precise signal. MPEP 2144(I): The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law.
In view of the discussion above, Examiner thus maintains the rejection of Claim 1, and dependents thereof, under 35 USC 103 as being unpatentable over at least Handique in view of Schnell and Breidenthal, as discussed above in the body of the rejection.
Conclusion
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.
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/B.J.K./Examiner, Art Unit 1798
/P. Kathryn Wright/Primary Examiner, Art Unit 1798
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