DETAILED CORRESPONDENCE
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 1/21/26 has been entered.
Response to Amendment
As to the amended specification and drawings, received on 12/16/25, the previous drawing objections are withdrawn.
As to the amended claims, received on 12/16/25, the previous 112(a) and 112(b) rejections are withdrawn.
Based on the amended claims and remarks, received on 12/16/25, the previous prior art rejections have been modified to address the claim amendments.
Claim Status
Claims 1, 3-16 are pending with claims 1, 3-6, 16 being examined and claims 7-15 deemed withdrawn.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 4-5, 16 are rejected under 35 U.S.C. 102a1/a2 as being anticipated by Tachibana et al (US 20160199840; hereinafter “Tachibana”; already of record).
As to claim 1, Tachibana teaches a method, comprising: receiving at a first end of a channel of a microfluidic device, a biologic sample including a nucleic acid, the channel disposed along a planar surface within the microfluidic device; warming a first subset of a plurality of heating elements disposed adjacent to the channel of the microfluidic device to a first particular temperature of a particular warming and cooling protocol and a second subset of the plurality of heating elements disposed adjacent to the channel of the microfluidic device to a second particular temperature of the particular warming and cooling protocol, the warming and cooling protocol associated with amplification of the nucleic acid; moving the biologic sample from the first end of the channel to a second end of the channel opposite the first end at a flow rate that is adjusted according to the warming and cooling protocol; and intermittently warming the biologic sample using the first subset of heating elements and the second subset of heating elements while the biologic sample moves from the first end of the channel to the second end of the channel (Tachibana teaches introducing a nucleic acid into a microchannel where there are different subsets of heaters 141/142 to warm the sample; [95, 97, 102, 103, 115-123], Fig. 5. Tachibana teaches that feed velocity of the sample/fluid is determined by pressure loss, which is the primary contributor to the feed velocity, and also that pressure loss is based on temperature; [174, 187]. Tachibana teaches in Fig. 11 that at 95 C that the pressure loss is less, due to increased heat and lower viscosity, so the feed velocity at a pressure loss of .4 is around 15 mm/s, while the feed velocity at a pressure loss of .4 at 60 C is around 7.5 mm/s. Therefore, Tachibana teaches that as the temperature increases that the feed velocity is increased/adjusted, and that as the temperature decreases that the feed velocity is decreased/adjusted. Tachibana also teaches adjusting the feed velocity; [328]. In Tachibana, adjusting the feed velocity (flow rate) based on temperature (which is related to pressure loss) would mean that the flow rate is adjusted based on temperature. The warming and cooling protocol have not been defined and because the prior art teaches adjusting flow rates at specific temperatures, then this is sufficient to serve as the warming and cooling protocol until further defined).
As to claim 4, Tachibana teaches the method of claim 1, including: warming the second subset of the plurality of heating elements to the second particular temperature of the particular warming and cooling protocol; and not warming a third set of elements disposed adjacent to the channel of the microfluidic device, the third set of elements associated with cooling zones of the microfluidic device (Tachibana teaches different subsets of heaters 141/142 to warm the sample; [95, 97, 102, 103, 115-123], Fig. 5. Tachibana does not teach the heaters are warming to a different temperature, so the heaters 141 on the left are the first subset and the heaters 141 on the right are the second subset, whereby the heaters 142 serve to cool; [131]. Alternatively, the heaters 141 on the left are the first subset and the heaters 142 on the left are the second subset, and the heaters 142 on the right are the third subset and serve to cool; [131]. Tachibana teaches a temperature control; Fig. 3, [204]).
As to claim 5, Tachibana teaches the method of claim 4, including digitally controlling and monitoring the temperature of the plurality of heating elements (Tachibana teaches a temperature control; Fig. 3, [121, 200, 204]).
As to claim 16, Tachibana teaches the method of claim 1, comprising adjusting the flow rate of the biologic sample according to the warming and cooling protocol by: adjusting the flow rate of the biologic sample according to a defined sequence of temperatures and a corresponding amount of time at which the biologic sample is held at a particular temperature in the sequence (Tachibana teaches introducing a nucleic acid into a microchannel where there are different subsets of heaters 141/142 to warm the sample; [95, 97, 102, 103, 115-123], Fig. 5. Tachibana teaches that feed velocity of the sample/fluid is determined by pressure loss, which is the primary contributor to the feed velocity, and also that pressure loss is based on temperature; [174, 187]. Tachibana teaches in Fig. 11 that at 95 C that the pressure loss is less, due to increased heat and lower viscosity, so the feed velocity at a pressure loss of .4 is around 15 mm/s, while the feed velocity at a pressure loss of .4 at 60 C is around 7.5 mm/s. Therefore, Tachibana teaches that as the temperature increases that the feed velocity is increased/adjusted, and that as the temperature decreases that the feed velocity is decreased/adjusted. Tachibana also teaches adjusting the feed velocity; [328]. In Tachibana, adjusting the feed velocity (flow rate) based on temperature (which is related to pressure loss) would mean that the flow rate is adjusted based on temperature. The warming and cooling protocol have not been defined and because the prior art teaches adjusting flow rates at specific temperatures, then this is sufficient to serve as the warming and cooling protocol until further defined).
Claims 1, 4-5, 16 are rejected under 35 U.S.C. 102a1/a2 as being anticipated by Cho et al (US 20100021972; hereinafter “Cho”; already of record).
As to claim 1, Cho teaches a method, comprising: receiving at a first end of a channel of a microfluidic device, a biologic sample including a nucleic acid, the channel disposed along a planar surface within the microfluidic device; warming a first subset of a plurality of heating elements disposed adjacent to the channel of the microfluidic device to a first particular temperature of a particular warming and cooling protocol and a second subset of the plurality of heating elements disposed adjacent to the channel of the microfluidic device to a second particular temperature of the particular warming and cooling protocol, the warming and cooling protocol associated with amplification of the nucleic acid; moving the biologic sample from the first end of the channel to a second end of the channel opposite the first end at a flow rate that is adjusted according to the warming and cooling protocol; and intermittently warming the biologic sample using the first subset of heating elements and the second subset of heating elements while the biologic sample moves from the first end of the channel to the second end of the channel (Cho teaches introducing nucleic acid into inlet, and flowing solution in channel 130, and multiple heaters in each region; [100, 105-108], Fig. 7. Cho teaches multiple heaters in each region; [74, 100, 105-108], Fig. 7. Cho teaches that the reaction rate is based on the flow rate; [13]. Cho also teaches that the flow rate of the input fluid, which interacts with the sample, is adjusted; [88, 91, 126]. Therefore, the fluid and corresponding sample have the flow rate adjusted such that the sample is associated with heating elements for defined times, as any time would be a defined time period. Additionally, standard samples are diluted to various concentrations and their flow rates are adjusted. In this respect, the standard sample that is created, with an adjusted flow rate is still considered a biologic sample. Because the reaction rate is based on the flow rate, and because Cho is performing defined PCR reactions at specific temperatures, then the reaction rate (and time) at specific temperatures would be related to and controlled by the flow rate, which Cho teaches as adjusting. The warming and cooling protocol have not been defined and because the prior art teaches adjusting flow rates at specific temperatures, then this is sufficient to serve as the warming and cooling protocol until further defined).
As to claim 4, Cho teaches the method of claim 1, including: warming the second subset of the plurality of heating elements to the second particular temperature of the particular warming and cooling protocol; and not warming a third set of elements disposed adjacent to the channel of the microfluidic device, the third set of elements associated with cooling zones of the microfluidic device (Cho teaches three different heating subset regions; [74, 100, 105-108], Fig. 7. Cho teaches that at least one of the heating regions is used to cool; [80, 82, 127, 129]).
As to claim 5, Cho teaches the method of claim 4, including digitally controlling and monitoring the temperature of the plurality of heating elements (Cho; [105-108]).
As to claim 16, Cho teaches the method of claim 1, comprising adjusting the flow rate of the biologic sample according to the warming and cooling protocol by: adjusting the flow rate of the biologic sample according to a defined sequence of temperatures and a corresponding amount of time at which the biologic sample is held at a particular temperature in the sequence (Cho teaches introducing nucleic acid into inlet, and flowing solution in channel 130, and multiple heaters in each region; [100, 105-108], Fig. 7. Cho teaches multiple heaters in each region; [74, 100, 105-108], Fig. 7. Cho teaches that the reaction rate is based on the flow rate; [13]. Cho also teaches that the flow rate of the input fluid, which interacts with the sample, is adjusted; [88, 91, 126]. Therefore, the fluid and corresponding sample have the flow rate adjusted such that the sample is associated with heating elements for defined times, as any time would be a defined time period. Additionally, standard samples are diluted to various concentrations and their flow rates are adjusted. In this respect, the standard sample that is created, with an adjusted flow rate is still considered a biologic sample. Because the reaction rate is based on the flow rate, and because Cho is performing defined PCR reactions at specific temperatures, then the reaction rate (and time) at specific temperatures would be related to and controlled by the flow rate, which Cho teaches as adjusting. The warming and cooling protocol have not been defined and because the prior art teaches adjusting flow rates at specific temperatures, then this is sufficient to serve as the warming and cooling protocol until further defined).
Claim Rejections - 35 USC § 103
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.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Tachibana et al (US 20160199840; hereinafter “Tachibana”; already of record) in view of Gale et al (US 20100167288; hereinafter “Gale”; already of record).
As to claim 3, Tachibana teaches the method of claim 1, and intermittently cooling, according to the particular warming and cooling protocol, the biologic sample.
Tachibana does not specifically teach cooling using a cooling agent flowing through a plurality of cooling chambers disposed adjacent to the channel. However, Gale teaches the analogous art of microfluidics that are heated and cooled for PCR, and using a cooling agent flowing through a plurality of cooling chambers disposed adjacent to the channel (Gale teaches cooling fins with cooling air that flows through; Fig. 1, [66]. Alternatively, Gale teaches water or forced fluid, or a refrigeration coil; [66]). It would have been obvious to one of ordinary skill in the art to have cooled the device of Tachibana using the cooling elements of Gale because Gale teaches that the cooling elements help to better cool the device to remove heat (Gale; [66]), and that there are various obvious ways to extract heat from the PCR device (Gale; [66]).
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Cho et al (US 20100021972; hereinafter “Cho”; already of record) in view of Beer et al (US 20090226971; hereinafter “Beer”; already of record).
As to claim 3, Cho teaches the method of claim 1, and intermittently cooling, according to the particular warming and cooling protocol, the biologic sample.
Cho does not specifically teach cooling using a cooling agent flowing through a plurality of cooling chambers disposed adjacent to the channel. However, Beer teaches the analogous art of microfluidics that are heated and cooled for PCR, and using a cooling agent flowing through a plurality of cooling chambers disposed adjacent to the channel (Beer teaches a cooler and cooling line through which cooling agent flows through; Fig. 1, [18, 38]). It would have been obvious to one of ordinary skill in the art to have cooled the device of Cho using the cooling elements of Beer because Beer teaches that the cooling elements help to better cool the device to remove heat (Beer; [38]), and that this helps to save time for temperature changes (Beer; [38]).
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Tachibana et al (US 20160199840; hereinafter “Tachibana”; already of record) in view of Wilding et al (WO93/22053; hereinafter “Wilding”; already of record).
As to claim 6, Tachibana teaches the method of claim 1, where the microfluidic device includes a first region with a plurality of heating elements and a second region including a plurality of heating elements, and where wherein intermittently warming the biologic sample using the first subset of heating elements and the second subset of heating elements includes cycling the biologic sample between the first region and the second region a specified number of times according to the warming and cooling protocol (Tachibana teaches moving the sample between the heating regions; see claim 1 above).
Tachibana does not specifically teach the different heating regions are chambers in which the sample is cycled between. However, Wilding teaches the analogous art of PCR in a microfluidic channel where the sample is cycled between various chambers at different temperatures (Wilding; Fig. 15, p. 32). It would have been obvious to one of ordinary skill in the art have modified the heating regions of Tachibana to be chambers as in Wilding because Wilding teaches that the chambers help to accommodate solution for cycling during PCR (Wilding; Fig. 15, p. 32).
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Cho et al (US 20100021972; hereinafter “Cho”; already of record) in view of Kornilovich et al (US 20120244604; hereinafter Kornilovich”; already of record).
As to claim 6, Cho teaches the method of claim 1, where the microfluidic device includes a first region with a plurality of heating elements and a second region including a plurality of heating elements, and where wherein intermittently warming the biologic sample using the first subset of heating elements and the second subset of heating elements includes cycling the biologic sample between the first region and the second region a specified number of times according to the warming and cooling protocol (Cho teaches moving the sample between the heating regions; see claim 1 above).
Cho does not specifically teach the different heating regions are chambers in which the sample is cycled between. However, Kornilovich teaches the analogous art of PCR in a microfluidic channel (Kornilovich; [27, 28]) where the sample is cycled between various chambers at different temperatures (Kornilovich; Fig. 2-4, [37-40]). It would have been obvious to one of ordinary skill in the art have modified the heating regions of Cho to be chambers as in Kornilovich because Kornilovich teaches that the chambers help to accommodate solution for cycling during PCR (Kornilovich; Fig. 2-4, [37-40]).
Claims 1, 4-5, 16 are alternatively rejected under 35 U.S.C. 103 as being unpatentable over Tachibana et al (US 20160199840; hereinafter “Tachibana”; already of record) in view of Ikeda, I (US 20090162929; hereinafter “Ikeda”; already of record).
As to claim 1, Tachibana teaches a method, comprising: receiving at a first end of a channel of a microfluidic device, a biologic sample including a nucleic acid, the channel disposed along a planar surface within the microfluidic device; warming a first subset of a plurality of heating elements disposed adjacent to the channel of the microfluidic device to a first particular temperature of a particular warming and cooling protocol and a second subset of the plurality of heating elements disposed adjacent to the channel of the microfluidic device to a second particular temperature of the particular warming and cooling protocol, the warming and cooling protocol associated with amplification of the nucleic acid; moving the biologic sample from the first end of the channel to a second end of the channel opposite the first end at a flow rate that is adjusted according to the warming and cooling protocol; and intermittently warming the biologic sample using the first subset of heating elements and the second subset of heating elements while the biologic sample moves from the first end of the channel to the second end of the channel (Tachibana teaches introducing a nucleic acid into a microchannel where there are different subsets of heaters 141/142 to warm the sample; [95, 97, 102, 103, 115-123], Fig. 5. Tachibana teaches that feed velocity of the sample/fluid is determined by pressure loss, which is the primary contributor to the feed velocity, and also that pressure loss is based on temperature; [174, 187]. Tachibana teaches in Fig. 11 that at 95 C that the pressure loss is less, due to increased heat and lower viscosity, so the feed velocity at a pressure loss of .4 is around 15 mm/s, while the feed velocity at a pressure loss of .4 at 60 C is around 7.5 mm/s. Therefore, Tachibana teaches that as the temperature increases that the feed velocity is increased/adjusted, and that as the temperature decreases that the feed velocity is decreased/adjusted. Tachibana also teaches adjusting the feed velocity; [328]. In Tachibana, adjusting the feed velocity (flow rate) based on temperature (which is related to pressure loss) would mean that the flow rate is adjusted based on temperature. The warming and cooling protocol have not been defined and because the prior art teaches adjusting flow rates at specific temperatures, then this is sufficient to serve as the warming and cooling protocol until further defined).
If it is deemed that Tachibana does not teach adjusting the flow rate, then Ikeda teaches the analogous art of a method for adjusting the temperature using various heaters in a microfluidic channel (Ikeda; abstract, Fig. 1, 2, 4-6) where the flow rate is known to be adjusted based on the nucleic acid length, the nucleic acid reaction rate, and other parameters, including temperature (Ikeda; [40]. Ikeda teaches that increasing flow rate can decrease the time at specific temperature zones and that specific temperature zones need differing times to perform the reactions; [54]. Ikeda teaches that flow rate and channel size can be controlled, because these parameters relate to the rection rate; [40]. Ikeda discloses that when subjecting samples to PCR that reaction times and temperatures are controlled so that the required reaction takes place [5, 23] (see also Fig. 2), and that the time for which the fluid flows may depend on the length of the channel [9, 50, 52]. Ikeda also discloses that it is known in the art to control the temperature and rate in order to achieve the required time for reactions [10].). Thus, with respect to adjusting the flow rate during PCR, it would have been obvious to a person having ordinary skill in the art to modify Tachibana’s sample flow rate to be adjusted as in Ikeda because Ikeda teaches that it is known to adjust the flow rate (Ikeda; [40]) and because Ikeda teaches that adjusting flow rate based on time at specific temperatures helps to ensure that samples are at the specific temperatures for the required time for reactions to take place (Ikeda; [5, 9, 10, 23, 50, 52, 54], Fig. 2). Ikeda teaches that flow rate is known to be adjusted based on the nucleic acid length, the nucleic acid reaction rate, and other parameters including channel length (Ikeda; [40]) and also that different reactions require different times (Ikeda; [5, 9, 10, 23, 50, 52, 54], Fig. 2). Therefore, it is evident that Ikeda recognizes that the flow rate is a result effective variable, and it would have been obvious to optimize Tachibana’s flow rate to be adjusted as in Ikeda depending on the nucleic acid length, the nucleic acid reaction rate, and other parameters as taught by Ikeda (Ikeda; [40]) and also to adjust the flow rates to ensure the samples were at the required temperature stage for the necessary time for the reaction to take place (Ikeda; [5, 9, 10, 23, 50, 52, 54], Fig. 2).
As to claim 4, modified Tachibana teaches the method of claim 1, including: warming the second subset of the plurality of heating elements to the second particular temperature of the particular warming and cooling protocol; and not warming a third set of elements disposed adjacent to the channel of the microfluidic device, the third set of elements associated with cooling zones of the microfluidic device (Tachibana teaches different subsets of heaters 141/142 to warm the sample; [95, 97, 102, 103, 115-123], Fig. 5. Tachibana does not teach the heaters are warming to a different temperature, so the heaters 141 on the left are the first subset and the heaters 141 on the right are the second subset, whereby the heaters 142 serve to cool; [131]. Alternatively, the heaters 141 on the left are the first subset and the heaters 142 on the left are the second subset, and the heaters 142 on the right are the third subset and serve to cool; [131]. Tachibana teaches a temperature control; Fig. 3, [204]).
As to claim 5, modified Tachibana teaches the method of claim 4, including digitally controlling and monitoring the temperature of the plurality of heating elements (Tachibana teaches a temperature control; Fig. 3, [121, 200, 204]).
As to claim 16, modified Tachibana teaches the method of claim 1, comprising adjusting the flow rate of the biologic sample according to the warming and cooling protocol by: adjusting the flow rate of the biologic sample according to a defined sequence of temperatures and a corresponding amount of time at which the biologic sample is held at a particular temperature in the sequence (The modification of the adjusting of the flow rate during PCR of Tachibana to have been adjusted based on time and reaction rates/temperatures as in Ikeda have already been discussed above. Ikeda; [40]. Ikeda teaches that increasing flow rate can decrease the time at specific temperature zones and that specific temperature zones need differing times to perform the reactions; [54]. Ikeda teaches that flow rate and channel size can be controlled, because these parameters relate to the rection rate; [40]. Ikeda discloses that when subjecting samples to PCR that reaction times and temperatures are controlled so that the required reaction takes place [5, 23] (see also Fig. 2), and that the time for which the fluid flows may depend on the length of the channel [9, 50, 52]. Ikeda also discloses that it is known in the art to control the temperature and rate in order to achieve the required time for reactions [10]).
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Tachibana et al (US 20160199840; hereinafter “Tachibana”; already of record) in view of Ikeda, I (US 20090162929; hereinafter “Ikeda”; already of record) in view of Gale et al (US 20100167288; hereinafter “Gale”; already of record).
As to claim 3, modified Tachibana teaches the method of claim 1, and intermittently cooling, according to the particular warming and cooling protocol, the biologic sample.
Modified Tachibana does not specifically teach cooling using a cooling agent flowing through a plurality of cooling chambers disposed adjacent to the channel. However, Gale teaches the analogous art of microfluidics that are heated and cooled for PCR, and using a cooling agent flowing through a plurality of cooling chambers disposed adjacent to the channel (Gale teaches cooling fins with cooling air that flows through; Fig. 1, [66]. Alternatively, Gale teaches water or forced fluid, or a refrigeration coil; [66]). It would have been obvious to one of ordinary skill in the art to have cooled the device of modified Tachibana using the cooling elements of Gale because Gale teaches that the cooling elements help to better cool the device to remove heat (Gale; [66]), and that there are various obvious ways to extract heat from the PCR device (Gale; [66]).
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Tachibana et al (US 20160199840; hereinafter “Tachibana”; already of record) in view of Ikeda, I (US 20090162929; hereinafter “Ikeda”) in view of Wilding et al (WO93/22053; hereinafter “Wilding”; already of record).
As to claim 6, modified Tachibana teaches the method of claim 1, where the microfluidic device includes a first region with a plurality of heating elements and a second region including a plurality of heating elements, and where wherein intermittently warming the biologic sample using the first subset of heating elements and the second subset of heating elements includes cycling the biologic sample between the first region and the second region a specified number of times according to the warming and cooling protocol (Tachibana teaches moving the sample between the heating regions; see claim 1 above).
Modified Tachibana does not specifically teach the different heating regions are chambers in which the sample is cycled between. However, Wilding teaches the analogous art of PCR in a microfluidic channel where the sample is cycled between various chambers at different temperatures (Wilding; Fig. 15, p. 32). It would have been obvious to one of ordinary skill in the art have modified the heating regions of modified Tachibana to be chambers as in Wilding because Wilding teaches that the chambers help to accommodate solution for cycling during PCR (Wilding; Fig. 15, p. 32).
Claims 1, 4-5, 16 are alternatively rejected under 35 U.S.C. 103 as being unpatentable over Cho et al (US 20100021972; hereinafter “Cho”; already of record) in view of Ikeda, I (US 20090162929; hereinafter “Ikeda”; already of record).
As to claim 1, Cho teaches a method, comprising: receiving at a first end of a channel of a microfluidic device, a biologic sample including a nucleic acid, the channel disposed along a planar surface within the microfluidic device; warming a first subset of a plurality of heating elements disposed adjacent to the channel of the microfluidic device to a first particular temperature of a particular warming and cooling protocol and a second subset of the plurality of heating elements disposed adjacent to the channel of the microfluidic device to a second particular temperature of the particular warming and cooling protocol, the warming and cooling protocol associated with amplification of the nucleic acid; moving the biologic sample from the first end of the channel to a second end of the channel opposite the first end at a flow rate that is adjusted according to the warming and cooling protocol; and intermittently warming the biologic sample using the first subset of heating elements and the second subset of heating elements while the biologic sample moves from the first end of the channel to the second end of the channel (Cho teaches introducing nucleic acid into inlet, and flowing solution in channel 130, and multiple heaters in each region; [100, 105-108], Fig. 7. Cho teaches multiple heaters in each region; [74, 100, 105-108], Fig. 7. Cho teaches that the reaction rate is based on the flow rate; [13]. Cho also teaches that the flow rate of the input fluid, which interacts with the sample, is adjusted; [88, 91, 126]. Therefore, the fluid and corresponding sample have the flow rate adjusted such that the sample is associated with heating elements for defined times, as any time would be a defined time period. Additionally, standard samples are diluted to various concentrations and their flow rates are adjusted. In this respect, the standard sample that is created, with an adjusted flow rate is still considered a biologic sample. Because the reaction rate is based on the flow rate, and because Cho is performing defined PCR reactions at specific temperatures, then the reaction rate (and time) at specific temperatures would be related to and controlled by the flow rate, which Cho teaches as adjusting. The warming and cooling protocol have not been defined and because the prior art teaches adjusting flow rates at specific temperatures, then this is sufficient to serve as the warming and cooling protocol until further defined).
If it is deemed that Cho does not teach adjusting the flow rate, then Ikeda teaches the analogous art of a method for adjusting the temperature using various heaters in a microfluidic channel (Ikeda; abstract, Fig. 1, 2, 4-6) where the flow rate is known to be adjusted based on the nucleic acid length, the nucleic acid reaction rate, and other parameters, including temperature (Ikeda; [40]. Ikeda teaches that increasing flow rate can decrease the time at specific temperature zones and that specific temperature zones need differing times to perform the reactions; [54]. Ikeda teaches that flow rate and channel size can be controlled, because these parameters relate to the rection rate; [40]. Ikeda discloses that when subjecting samples to PCR that reaction times and temperatures are controlled so that the required reaction takes place [5, 23] (see also Fig. 2), and that the time for which the fluid flows may depend on the length of the channel [9, 50, 52]. Ikeda also discloses that it is known in the art to control the temperature and rate in order to achieve the required time for reactions [10].). Thus, with respect to adjusting the flow rate during PCR, it would have been obvious to a person having ordinary skill in the art to modify Cho sample flow rate to be adjusted as in Ikeda because Ikeda teaches that it is known to adjust the flow rate (Ikeda; [40]) and because Ikeda teaches that adjusting flow rate based on time at specific temperatures helps to ensure that samples are at the specific temperatures for the required time for reactions to take place (Ikeda; [5, 9, 10, 23, 50, 52, 54], Fig. 2). Ikeda teaches that flow rate is known to be adjusted based on the nucleic acid length, the nucleic acid reaction rate, and other parameters including channel length (Ikeda; [40]) and also that different reactions require different times (Ikeda; [5, 9, 10, 23, 50, 52, 54], Fig. 2). Therefore, it is evident that Ikeda recognizes that the flow rate is a result effective variable, and it would have been obvious to optimize Cho flow rate to be adjusted as in Ikeda depending on the nucleic acid length, the nucleic acid reaction rate, and other parameters as taught by Ikeda (Ikeda; [40]) and also to adjust the flow rates to ensure the samples were at the required temperature stage for the necessary time for the reaction to take place (Ikeda; [5, 9, 10, 23, 50, 52, 54], Fig. 2).
As to claim 4, modified Cho teaches the method of claim 1, including: warming the second subset of the plurality of heating elements to the second particular temperature of the particular warming and cooling protocol; and not warming a third set of elements disposed adjacent to the channel of the microfluidic device, the third set of elements associated with cooling zones of the microfluidic device (Cho teaches three different heating subset regions; [74, 100, 105-108], Fig. 7. Cho teaches that at least one of the heating regions is used to cool; [80, 82, 127, 129]).
As to claim 5, modified Cho teaches the method of claim 4, including digitally controlling and monitoring the temperature of the plurality of heating elements (Cho; [105-108]).
As to claim 16, modified Cho teaches the method of claim 1, comprising adjusting the flow rate of the biologic sample according to the warming and cooling protocol by: adjusting the flow rate of the biologic sample according to a defined sequence of temperatures and a corresponding amount of time at which the biologic sample is held at a particular temperature in the sequence (The modification of the adjusting of the flow rate during PCR of Cho to have been adjusted based on time and reaction rates/temperatures as in Ikeda have already been discussed above. Ikeda; [40]. Ikeda teaches that increasing flow rate can decrease the time at specific temperature zones and that specific temperature zones need differing times to perform the reactions; [54]. Ikeda teaches that flow rate and channel size can be controlled, because these parameters relate to the rection rate; [40]. Ikeda discloses that when subjecting samples to PCR that reaction times and temperatures are controlled so that the required reaction takes place [5, 23] (see also Fig. 2), and that the time for which the fluid flows may depend on the length of the channel [9, 50, 52]. Ikeda also discloses that it is known in the art to control the temperature and rate in order to achieve the required time for reactions [10]).
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Cho et al (US 20100021972; hereinafter “Cho”; already of record) in view of Ikeda, I (US 20090162929; hereinafter “Ikeda”; already of record) in view of Beer et al (US 20090226971; hereinafter “Beer”; already of record).
As to claim 3, modified Cho teaches the method of claim 1, and intermittently cooling, according to the particular warming and cooling protocol, the biologic sample.
Modified Cho does not specifically teach cooling using a cooling agent flowing through a plurality of cooling chambers disposed adjacent to the channel. However, Beer teaches the analogous art of microfluidics that are heated and cooled for PCR, and using a cooling agent flowing through a plurality of cooling chambers disposed adjacent to the channel (Beer teaches a cooler and cooling line through which cooling agent flows through; Fig. 1, [18, 38]). It would have been obvious to one of ordinary skill in the art to have cooled the device of modified Cho using the cooling elements of Beer because Beer teaches that the cooling elements help to better cool the device to remove heat (Beer; [38]), and that this helps to save time for temperature changes (Beer; [38]).
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Cho et al (US 20100021972; hereinafter “Cho”; already of record) in view of Ikeda, I (US 20090162929; hereinafter “Ikeda”; already of record) in view of Kornilovich et al (US 20120244604; hereinafter Kornilovich”; already of record).
As to claim 6, modified Cho teaches the method of claim 1, where the microfluidic device includes a first region with a plurality of heating elements and a second region including a plurality of heating elements, and where wherein intermittently warming the biologic sample using the first subset of heating elements and the second subset of heating elements includes cycling the biologic sample between the first region and the second region a specified number of times according to the warming and cooling protocol (Cho teaches moving the sample between the heating regions; see claim 1 above).
Modified Cho does not specifically teach the different heating regions are chambers in which the sample is cycled between. However, Kornilovich teaches the analogous art of PCR in a microfluidic channel (Kornilovich; [27, 28]) where the sample is cycled between various chambers at different temperatures (Kornilovich; Fig. 2-4, [37-40]). It would have been obvious to one of ordinary skill in the art have modified the heating regions of modified Cho to be chambers as in Kornilovich because Kornilovich teaches that the chambers help to accommodate solution for cycling during PCR (Kornilovich; Fig. 2-4, [37-40]).
Response to Arguments
Applicant’s arguments filed on 12/16/25 have been considered, but they are not persuasive and the arguments will be addressed below in order to advance prosecution.
Applicants argue on pages 8-9 of their remarks that Tachibana does not specifically teach or suggest the flow rate that is adjusted according to the warming and cooling protocol. Tachibana teaches introducing a nucleic acid into a microchannel where there are different subsets of heaters 141/142 to warm the sample; [95, 97, 102, 103, 115-123], Fig. 5. Tachibana teaches that feed velocity of the sample/fluid is determined by pressure loss, which is the primary contributor to the feed velocity, and also that pressure loss is based on temperature; [174, 187]. Tachibana teaches in Fig. 11 that at 95 C that the pressure loss is less, due to increased heat and lower viscosity, so the feed velocity at a pressure loss of .4 is around 15 mm/s, while the feed velocity at a pressure loss of .4 at 60 C is around 7.5 mm/s. Therefore, Tachibana teaches that as the temperature increases that the feed velocity is increased/adjusted, and that as the temperature decreases that the feed velocity is decreased/adjusted. Tachibana also teaches adjusting the feed velocity; [328]. In Tachibana, adjusting the feed velocity (flow rate) based on temperature (which is related to pressure loss) would mean that the flow rate is adjusted based on temperature. The warming and cooling protocol have not been defined and because the prior art teaches adjusting flow rates at specific temperatures, then this is sufficient to serve as the warming and cooling protocol until further defined.
Applicants argue on page 10 of their remarks that although Cho does not specifically teach or suggest the flow rate that is adjusted according to the warming and cooling protocol. However, the examiner respectfully disagrees. Cho teaches introducing nucleic acid into inlet, and flowing solution in channel 130, and multiple heaters in each region; [100, 105-108], Fig. 7. Cho teaches multiple heaters in each region; [74, 100, 105-108], Fig. 7. Cho teaches that the reaction rate is based on the flow rate; [13]. Cho also teaches that the flow rate of the input fluid, which interacts with the sample, is adjusted; [88, 91, 126]. Therefore, the fluid and corresponding sample have the flow rate adjusted such that the sample is associated with heating elements for defined times, as any time would be a defined time period. Additionally, standard samples are diluted to various concentrations and their flow rates are adjusted. In this respect, the standard sample that is created, with an adjusted flow rate is still considered a biologic sample. Because the reaction rate is based on the flow rate, and because Cho is performing defined PCR reactions at specific temperatures, then the reaction rate (and time) at specific temperatures would be related to and controlled by the flow rate, which Cho teaches as adjusting. The warming and cooling protocol have not been defined and because the prior art teaches adjusting flow rates at specific temperatures, then this is sufficient to serve as the warming and cooling protocol until further defined.
Applicants do not provide any arguments with respect to rejections based on Idkeda, and therefore those rejection(s) remain.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BENJAMIN R WHATLEY whose telephone number is (571)272-9892. The examiner can normally be reached Mon- Fri 8am-5pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Charles Capozzi can be reached at (571) 270-3638. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/BENJAMIN R WHATLEY/Primary Examiner, Art Unit 1798
Prosecution Insights