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
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 03/28/2025 has been entered.
Status of the Claims
Claims 1 and 21 have been amended. Claim 19 was previously withdrawn. Claims 1-19 and 21 are currently pending and claims 1-18 and 21 are examined herein.
Status of the Rejection
The claim objections have been overcome by the applicant's amendments.
All 35 U.S.C. § 103 rejections from the previous office action are essentially maintained and modified only in response to the amendments to the claims.
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.
Claim(s) 1-3, 6-7, 10-13, and 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Davalos et al. (US-20080105565-A1) in view of Peng et al. (US-20140027287-A1), Ding et al. (Concentration of Sindbis virus with optimized gradient insulator-based dielectrophoresis, 2016, Analyst, 141, 1997-2008) and Zenhausern et al. (US20040011650A1).
Regarding claim 1, a system comprising: an insulator-based dielectrophoresis device (Davalos teaches a system comprising an insulator-based dielectrophoresis device [iDEP], Para. 0003) comprising
(i) a fluid flow channel defined by a first substrate surface and a second substrate surface spaced from the first substrate surface (Davalos teaches a fluid flow channel 101 defined by a first substrate surface and a second substrate surface spaced from the first substrate surface [opposing surfaces/walls in a channel which are spaced apart from each other], Para. 0014 and Figure 1. The opposing surfaces/walls in a channel meet the limitation of a first substrate surface and a second substrate surface as evidenced by the instant specification which recites the first and second substrate surface 22, 24 may be formed on the same substrate 11 (e.g., opposing surfaces in a channel) [Para. 0034 of the instant specification]), the fluid flow channel having at least one fluid inlet and at least one fluid outlet (Davalos teaches the fluid flow channel 101 has at least one fluid inlet 103a and at least one fluid outlet 104, Figure 1 and Para. 0053),
(ii) at least one insulating flow structure extending from the first substrate surface toward the second substrate surface thereby defining a constriction in the fluid flow channel between the first substrate surface and the second substrate surface (Davalos teaches at least one insulating flow structure 105a extending from the first substrate surface toward the second substrate surface [the insulating structure is on or in at least one wall of the microchannel and thus extends from the first substrate surface/microchannel wall toward the second substrate surface/opposing microchannel wall], thereby defining a constriction [the area/spaces between the insulating structures 105a] in the fluid flow channel 101 between the first substrate surface/microchannel wall and the second substrate surface/opposing microchannel wall, Figure 1 and Para. 0014, 0038, and 0041);
electrodes in electrical communication with the at least one fluid inlet and the at least one fluid outlet of the fluid flow channel (Davalos teaches electrodes in electrical communication with the at least one fluid inlet 103a and the at least one fluid outlet 104 of the fluid flow channel 101 [the electrode connected to microchannel inlet 103a is connected to a positive voltage terminal and the electrode connected to microchannel outlet 104 is electrically grounded], Figure 1 and Para. 0053), the limitation “wherein the electrodes are positioned to generate a spatially non-uniform electric field across the at least one insulating flow structure of the fluid flow channel to exert a dielectrophoretic force on the one or more analytes suspended in the fluid within the fluid flow channel” is a functional recitation. Apparatus claims cover what a device is, not what a device does [MPEP 2114(II)]. A functional recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. See MPEP 2114. In the instant case, Davalos teaches the above electrodes that are specifically configured to perform the functional limitations above (Davalos teaches the electrodes are positioned to generate a spatially non-uniform electric field across the insulating flow structure 105a of the fluid flow channel 101, since the electrodes provide an electric field and the electric field is made non-uniform by the insulating structures on or in the wall of the microchannel, Para. 0038 and 0042. This exerts a dielectrophoretic force on the one or more analytes suspended in the fluid within the fluid flow channel 101 in which different species of analytes can be by separated or concentrated using iDEP, Para. 0035-0036, 0038, 0042, 0045, and 0076);
a power supply connected to each of the electrodes to generate an electric field within the fluid flow channel (Davalos teaches a power supply connected to each of the electrodes at the microchannel inlets 103a and 104 to supply a voltage [corresponding to an electric field] to electrodes for iDEP within the fluid flow channel 101, and thus generates an electric field within the fluid flow channel, Para. 0076-0077 and 0071, Figure 1; Fig.7 shows an AC power source [Para. 0080]), and
PNG
media_image1.png
500
752
media_image1.png
Greyscale
a detection chamber placed in fluid communication with the fluid flow channel by an opening in either the first substrate surface or the second substrate surface, wherein the opening is configured downstream of the at least one insulating flow structure (Davalos teaches a detection area 109 and the area after 106 to port 108 including detection area 109 corresponding to the detection chamber [concentrated analytes move through area 106 to port 108 through a detection area 109, Para. 0054 and see annotated Fig. 1 of Davalos above] placed in fluid communication with the fluid flow channel 101 by an opening in either the first substrate surface/wall or the second substrate surface/wall, wherein the opening is configured downstream [on the right of] the at least one insulating flow structure 105a, Figure 1 and Para. 0054), wherein the detection chamber includes an electrochemical sensor (Davalos teaches the detection chamber [the area after area 106 to port 108, see annotated Fig. 1 of Davalos above] includes an electrochemical sensor, which is the area after 106 to detection area 109 with sensing electrodes 110a and 110b [see annotated Fig. 1 of Davalos above], the limitation “configured to constrict a flow of a fluid entering the detection chamber” is a functional recitation. Apparatus claims cover what a device is, not what a device does [MPEP 2114(II)]. A functional recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. See MPEP 2114. In the instant case, Davalos teaches the above electrochemical sensor as seen in annotated Fig. 1 that is specifically configured to perform the functional limitations above (Davalos teaches the electrochemical sensor which is the area after 106 to 109 with sensing electrodes 110a and 110b configured to constrict the flow of fluid entering the detection chamber [the area after area 106 to port 108], since the area after 106 to detection area 109 is constricted/much smaller than the channel 101, it is configured to constrict the flow of fluid entering the detection chamber [the area after area 106 to port 108], see annotated Figure 1 above and Para. 0054);
Davalos is silent to through a pore, wherein the pore is sized to produce a detectable signal upon passage of one or more analytes through the pore. However, Davalos teaches a detectable signal [impedance] is produced upon passage of one or more analytes through the detection area 109 (Para. 0054 and Figure 1).
Peng teaches a device where the capture rate of molecules in a nanopore is increased via dielectrophoresis [Para. 0002]. Peng further teaches an electrochemical sensor/device 101 configured to constrict the flow of fluid entering the detection chamber/fluidic cell 114 through a nanopore 103 and the nanopore 103 separates a first chamber [microfluidic channel 102 from a second chamber [fluidic channel 114] (Para. 0023, 0038 and Figures 1-2). Additionally, Peng teaches the nanopore is sized [nm size] to produce a detectable signal [a measured ionic current] upon passage of one or more analytes/molecules 119 through the nanopore 103, where the molecule 119 changes/affects the ionic current, Para. 0023 and Figures 1-2. This configuration is beneficial since it allows for characterizing the molecule 119 while in the nanopore and can be used for sequencing biological samples, such as DNA [Para. 0023 and 0014].
Davalos and Peng are considered analogous art to the claimed invention, because they are in the same field of microfluidic devices using dielectrophoresis [see e.g., Para. 0002 of Peng and Abstract of Davalos]. It would have been obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to modify the detection area and electrochemical sensor of Davalos to include a nanopore where the flow of fluid is constricted entering the detection chamber through a pore and which is sized to produce a detectable signal upon passage of one or more analytes through the pore, as taught by Peng, since Peng teaches this configuration would be beneficial for characterizing an analyte/molecule while in the nanopore and for sequencing biological samples, such as DNA [Para. 0023 and 0014 of Peng]. Furthermore, the claimed limitations are obvious because all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results, MPEP 2143[I][A].
Modified Davalos is silent to a valve positioned in the opening, the valve being movable from a closed position to an open position to allow passage of the one or more analytes into the detection chamber.
Ding teaches an insulator-based DEP device used in the field of separation and manipulation of bioparticles such as DNA, protein and viruses [Abstract]. Ding further teaches the insulator-based DEP device that includes triangular insulating wall protrusions [corresponding to insulating flow structures] may be improved by integrating orthogonal side channels and valves onto the main channel [corresponding to a valve positioned in an opening, i.e., between the main channel and the orthogonal side channel], which would be beneficial for realizing the controlled delivery of concentrated samples [Fig. 1 and Page 2006, Col. 2, Para. 2]. With valves, the side channels can be held electrically silent during capture and be activated to transport the concentrated analyte to further analysis, yielding a rapid response technique that benefits clinical diagnostics/detection [Page 2006, Col. 2, Para. 2].
Zenhausern teaches devices for manipulating analytes via dielectrophoresis to allow for improved detection of target analytes [Abstract]. Zenhausern discloses the device can include at least one fluid valve that can control the flow of fluid into or out of a module of the device, or divert the flow into one or more channels [Para. 0079]. A variety of valves may be used including valves that can be opened and closed, corresponding to a valve being movable from a closed position to an open position [Para. 0081].
Given the teachings of Ding regarding integrating orthogonal side channels and valves onto the main channel [corresponding to a valve positioned in an opening, i.e., between the main channel and the orthogonal side channel] [Page 2006, Col. 2, Para. 2 of Ding] and Zenhausern regarding including at least one fluid valve for controlling the flow of fluid into or out of a module of the device, or divert the flow into one or more channels where the valve can be opened and closed [Para. 0079 and 0081 of Zenhausern], it would have been obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to modify the iDEP device of modified Davalos to provide a valve positioned in the opening, the valve being movable from a closed position to an open position, as taught by Ding and Zenhausern, since Ding teaches it would be beneficial for realizing the controlled delivery of concentrated samples and with valves, the side channels can be held electrically silent during capture and be activated to transport the concentrated analyte to further analysis, yielding a rapid response technique that benefits clinical diagnostics/detection [Page 2006, Col. 2, Para. 2 of Ding] and Zenhausern teaches it would be beneficial for controlling the flow of fluid into or out of a module of the device, or diverting the flow into one or more channels [Para. 0079 of Zenhausern]. Furthermore, the claimed limitations are obvious because all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results, MPEP 2143[I][A].
The limitation “to allow passage of the one or more analytes into the detection chamber” is a functional recitation. Apparatus claims cover what a device is, not what a device does [MPEP 2114(II)]. A functional recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. See MPEP 2114. In the instant case, modified Davalos as outlined above yields a valve that is specifically configured to perform the functional limitations above (Modified Davalos as outlined above yields a valve that can be opened or closed for controlling the flow of fluid [including the one or more analytes] into or out of a module of the device or into one or more channels [corresponding to the detection chamber] [Para. 0079 and 0081 of Zenhausern], and is positioned at the opening for realizing the controlled delivery of concentrated samples and with the valve, the side channels [corresponding to the channel leading to the detection chamber] can be held electrically silent during capture and be activated to transport the concentrated analyte to further analysis [Fig. 1 and Page 2006, Col. 2, Para. 2 of Ding]. Thus, the valve of modified Davalos is specifically configured to allow the passage of the one or more analytes into the detection chamber]).
an additional electrode positioned in the detection chamber (Davalos teaches an additional electrode positioned in port 108 [Paras. 0053-0054 of Davalos], and thus the electrode is positioned in the detection chamber which includes the area after 106 to port 108 as outlined in the rejection above [see annotated Fig. 1 of Davalos above, Paras. 0053-0054 of Davalos]
the limitation “the additional electrode biasing the spatially non-uniform electric field between the additional electrode and one of the electrodes in electrical communication with the at least one fluid inlet or biasing the spatially non-uniform electric field between the additional electrode and another of the electrodes in electrical communication with the at least one fluid outlet of the fluid flow channel” is a functional recitation. Apparatus claims cover what a device is, not what a device does [MPEP 2114(II)]. A functional recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. See MPEP 2114. In the instant case, Davalos teaches the above additional electrode positioned in port 108 and the detection chamber as seen in annotated Fig. 1 that is specifically configured to perform the functional limitations above (Davalos teaches the electrode at port 108 are allowed to float, and to divert the concentrated analytes through the detection area 109, the voltage at the inlet 104 is raised, then the voltage at port 108 is changed from floating to ground, thereby causing the concentrated analytes to move through area 106 to port 108 through a detection area 109 [Paras. 0053-0054 of Davalos]. Davalos further teaches the voltage at the electrode in the microfluidic inlet 103a was set to a threshold level (Vth), while the electrode at port 108 was set to ground [Para. 0078 of Davalos]. Thus, the electrode at port 108 [the additional electrode in the detection chamber] biases the spatially non-uniform electric field by applying a voltage between the additional electrode and one of the electrodes in electrical communication with the at least one fluid inlet [the electrode in the microfluidic inlet 103a] across the insulating flow structure 105a, since the electrodes provide an electric field and the electric field is made non-uniform by the insulating structures on or in the wall of the microchannel. Additionally, different non-uniform electric fields may also be induced by application of different electrical currents [Para. 0045]. Therefore, the electrode at port 108 [the additional electrode in the detection chamber] is capable of and specifically configured to perform the functional limitations above [Para. 0035-0036, 0038, 0042, 0045, 0053-0054, 0078 and 0076 of Davalos]).
Regarding claim 2, the system of claim 1, wherein the pore is a nanopore (Modified Davalos as applied to claim 1 above teaches the pore is a nanopore [Para. 0022 of Peng]).
Regarding claim 3, the system of claim 2, wherein the nanopore has a diameter that is no more 100 nm wide in diameter, or no more than 50 nm wide in diameter, or no more than 40 nm wide in diameter, or no more than 30 nm wide in diameter, or no more than 20 nm wide in diameter, or no more than 10 nm wide in diameter (Modified Davalos as applied to claim 2 above teaches the nanopore has a diameter of sub-nm to 100 nm, falling within the claimed range of no more than 100 nm in diameter [Para. 0022 of Peng]).
Regarding claim 6, the system of claim 1, wherein the at least one insulating flow structure includes a first insulating flow structure and a second insulating flow structure, and wherein the detection chamber is positioned between the first insulation flow structure and the second insulating flow structure (Davalos teaches the at least one insulating flow structure includes a first insulating flow structure 105a and a second insulating flow structure 105b, and wherein the detection chamber [the area after area 106 to port 108, see annotated Fig. 1 of Davalos above] is positioned between the first insulating flow structure 105a and the second insulating flow structure 105b, Figure 1 and Paras. 0053 -0054).
Regarding claim 7, the system of claim 1, wherein the electrochemical sensor includes a substrate formed from a material selected from a polymer, silicon nitride, graphene, or molybdenum disulfide (Davalos teaches the iDEP device and the microfluidic channels are made of a polymer, and thus the electrochemical sensor [the area after 106 to detection area 109 with sensing electrodes 110a and 110b] includes a substrate formed from a polymer, Para. 0023 and 0032 of Davalos).
Regarding claim 10, the system of claim 1, the limitation “wherein the at least one insulating flow structure is configured to selectively separate a first analyte from the fluid, and allows passage of a second analyte” is a functional recitation. Apparatus claims cover what a device is, not what a device does [MPEP 2114(II)]. A functional recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. See MPEP 2114. In the instant case, Davalos teaches the insulating flow structure 105a as seen in Figure 1 that is specifically configured to perform the functional limitations above (Davalos teaches the first array of insulating flow structure 105a which can selectively separate a first species of analyte from the second species of analyte from the fluid, at a voltage which traps one/first species of analyte without trapping the second species of analyte and thus would allow passage of a second analyte, Para. 0036 and 0044, Figure 1).
Regarding claim 11, the system of claim 1, wherein the at least one insulating flow structure includes a plurality of insulating flow structures in the fluid flow channel, wherein each of the plurality of insulating flow structures are configured to form a constriction in the fluid flow channel (Davalos teaches the at least one insulating flow structure includes a plurality of insulating flow structures 105a, 105b in the fluid flow channel 101, wherein each of the plurality of the insulating flow structures 105a, 105b are configured to form a constriction [the area/spaces within each array of the insulating flow structures 105a. 105b] in the fluid flow channel 101, Figure 1 and Para. 0040 and 0053).
Regarding claim 12, the system of claim 11, wherein the plurality of insulating flow structures includes a first insulating flow structure and a second insulating flow structure, wherein the first insulating flow structure and the second insulating flow structure each have a constriction (Davalos teaches the plurality of insulating flow structures 105a, 105b includes a first insulating flow structure 105a and a second insulating flow structure 105b, wherein the first insulating flow structure 105a and the second insulating flow structure 105b each have a constriction [the area/spaces within each array of the insulating flow structures 105a. 105b], Figure 1 and Para. 0053); the limitation “a first insulating flow structure configured to selectively separate a first analyte from the fluid flow channel, and a second insulating flow structure configured to selectively separate a second analyte from the fluid flow channel, wherein the first insulating flow structure and the second insulating flow structure each have a constriction that allows passage of a third analyte” is a functional recitation. Apparatus claims cover what a device is, not what a device does [MPEP 2114(II)]. A functional recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. See MPEP 2114. In the instant case, Davalos teaches the above first insulating flow structure 105a and the second insulating flow structure 105b as seen in Figure 1 that are specifically configured to perform the functional limitations above (Davalos teaches the first array of insulating flow structure 105a can comprise insulating structures different from those of the second array of insulating flow structure 105b such that the differences create different non-uniform electric fields which separate and concentrate analytes of different species [Para. 0044-0045]. Thus, the first array of insulating flow structure 105a is capable of selectively separating a first analyte from the fluid flow channel and the second array of insulating flow structure 105b is capable of selectively separating a second analyte from the fluid flow channel. Furthermore, Davalos teaches different trapping sites which are tailored to trap one species over another [one set of posts traps species B and the other set traps A and C or A, B, and C] and thus if it is capable of trapping a third analyte, it is capable of allowing passage of a third analyte as the insulating structures are specifically configured to allow passage of a specific analyte of interest through the constrictions, Para. 0044-0045, Figure 1).
Regarding claim 13, the system of claim 1, wherein the fluid flow channel is a microchannel or a nanochannel (Davalos teaches the fluid flow channel 101 is a microchannel, Para. 0053).
Regarding claim 18, the system of claim 1 comprising an array of electrochemical sensors (Davalos teaches an array of electrochemical sensors and detection areas 109, 111, including electrodes 110a, 110b and 112a, 112b, respectively, which are above and below the microchannel 101, Para. 0054 and Figure 1), the limitation “each configured to constrict the flow of fluid in the fluid flow channel” is a functional recitation. Apparatus claims cover what a device is, not what a device does [MPEP 2114(II)]. A functional recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. See MPEP 2114. In the instant case, Davalos teaches the above array of electrochemical sensors as seen in Fig. 1 that is specifically configured to perform the functional limitations above (Davalos teaches the array of electrochemical sensor and detection areas 109, 111 [which is the area after 106 to 109 with sensing electrodes 110a and 110b for the first electrochemical sensor and the area between 106 and 107 with sensing electrodes 112a, 112b for the second electrochemical sensor] configured to constrict the flow of fluid entering the detection chambers 109, 111, since the area after 106 to 109 and the area between 106 and 107 is constricted/much smaller than the channel 101, it is configured to constrict the flow of fluid entering the detection area 109 and 111, and thus constricts the flow of fluid in the fluid flow channel, Figure 1 and Para. 0054);
Modified Davalos is silent to through a respective pore, wherein the respective pore is sized to produce a detectable signal upon passage of an analyte through the pore. However, modified Davalos as applied to claim 1 above teaches the first electrochemical sensor and detection area 109 includes a nanopore where the flow of fluid in the fluid flow channel is constricted through the nanopore and the nanopore is sized to produce a detectable signal upon passage of an analyte through the nanopore [Para. 0023, 0038 and Figures 1-2 of Peng].
Davalos further teaches a second sample or analyte can be detected at the second electrochemical sensor and detection region 111, [Para. 0054 and Figure 1 of Davalos].
It would have been obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to modify the second electrochemical sensor and detection area 111 of modified Davalos to include a nanopore where the flow of fluid is constricted upon entering the detection chamber through a respective pore and which is sized to produce a detectable signal upon passage of an analyte through the pore, as taught by Peng, since Peng teaches this configuration would be beneficial for characterizing an analyte/molecule while in the nanopore and for sequencing biological samples, such as DNA [Para. 0023 and 0014 of Peng]. Furthermore, the claimed limitations are obvious because all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results, MPEP 2143[I][A].
Claim(s) 4-5 are rejected under 35 U.S.C. 103 as being unpatentable over Davalos in view of Peng, Ding, and Zenhausern, as applied to claim 1 above, and further in view of Liu et al. (Selective Individual Primary Cell Capture Using Locally Bio-Functionalized Micropores, 2013, PLOS One, Volume 8, Issue 3, Pages 1-8).
Regarding claim 4, modified Davalos is silent to wherein the pore is a micropore.
Liu teaches a micropore chip for the sensing of biological targets (Abstract and Figures 1 – 3). Liu specifically teaches a micropore with a 15 μm diameter can be used for sensing large analytes such as cells and translocating through the pore for sensing based on a variation of ionic current across the micropore verses time [Abstract, Figures 1-3 and Page 2, Col. 2, last paragraph].
Modified Davalos and Liu are considered analogous art to the claimed invention because they are in the same field of biological sensors. It would have been obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to substitute the nanopore of modified Davalos with a micropore that has a diameter of 15 μm as taught by Liu, since Liu teaches this configuration would be beneficial for sensing large analytes and translocating through the pore for sensing based on a variation of ionic current across the micropore verses time [Abstract, Figures 1-3 3 and Page 2, Col. 2, last paragraph of Liu]. Furthermore, the claimed limitations are obvious because the substitution of one known element for another yields predictable results to one of ordinary skill in the arts (MPEP 2143[I][B]).
Regarding claim 5, the system of claim 4, wherein the micropore has a diameter that is no more than 100 μm in diameter, or no more than 50 μm wide in diameter, or no more than 40 μm wide in diameter, or no more than 30 μm wide in diameter, or no more than 20 μm wide in diameter, or no more than 10 μm wide in diameter (Modified Davalos as outlined in the rejection of claim 4 above yields a micropore with a diameter that is 15 μm, falling within the claimed range of no more than 100 μm in diameter [Liu: Figure 1 and Page 2, Col. 2, Para. 1 Results and Discussion].
Claim(s) 8-9 are rejected under 35 U.S.C. 103 as being unpatentable over Davalos in view of Peng, Ding, and Zenhausern, as applied to claim 1 above, and further in view of Chuah et al. (Nanopore blockade sensors for ultrasensitive detection of proteins in complex biological samples, 2019, Nature Communications, 10, Pages 1-9).
Regarding claim 8, modified Davalos is silent to wherein the pore includes a functional group coupled to a surface of the pore.
Chuah teaches a nanopore sensor for detecting individual species passing through a nanoscale pore (Abstract and Figure 1). Chuah further teaches the nanopore includes a functional group of an antibody [which is a protein] coupled to the surface of the nanopore by chemical modification (Figure 1a and Page 8, Col. 1, Para. 1-2). The antibody functionalized nanopore is beneficial for capturing analytes and improving analyte specificity in nanopore sensors [Abstract and Page 2, Col. 2, Para. 1].
Modified Davalos and Chuah are considered analogous art to the claimed invention because they are in the same field of biological sensors. It would have been obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to modify the nanopore of modified Davalos to include an antibody functional group functionalized/coupled to the surface of the pore, as taught by Chuah, since Chuah teaches this would be beneficial for capturing analytes and improving analyte specificity in nanopore sensors [Abstract and Page 2, Col. 2, Para. 1 of Chuah]. Furthermore, the claimed limitations are obvious because all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results, MPEP 2143[I][A].
Regarding claim 9, the system of claim 8, wherein the functional group is an organic molecule, a protein, or a material compatible with atomic layer deposition selected from HfO2, TiO2, a sulfide, alumina, a silicate, a perovskite, or combinations thereof (Modified Davalos as outlined in the rejection of claim 8 above yields a functional group which is an antibody [corresponding to a protein] [Abstract, Figure 1a and Page 8, Col. 1, Para. 1-2 of Chuah].
Claim(s) 14 – 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Davalos in view of Peng, Ding, and Zenhausern as applied to claim 1 above, and further in view of Zhu et al. (US-20150028846-A1).
Regarding claim 14, modified Davalos is silent to further including a control system in electrical communication with a memory, the electrochemical sensor, the electrodes, and the power supply, the control system configured to execute instructions stored within the memory to cause the control system to: detect the detectable signal produced from the one or more analytes passing through the pore of the electrochemical sensor; and output a metric indicative of the one or more analytes based on the detectable signal.
Peng teaches a control system 500 [a computer] in electrical communication with a memory 520, the electrochemical sensor/nanodevice, the electrodes and electric fields and the power supply [voltage source], Figures 4-5 and Para. 0047-0048. Peng further teaches the control system is configured to execute software/instructions stored within the memory 520 [Para. 0049] that causes the control system 500 to read, display, view and record the ionic current [the detectable signal] for each molecule passing through the pore of the electrochemical sensor/nanodevice [Para. 0047-0049 and 0023-0026, Figures 1 and 5]. This configuration is beneficial since it can be used for testing and analysis [Para. 0047].
It would have been obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to modify the system and iDEP device including the electrochemical sensor and detection area 109 modified with a nanopore, electrodes and power supply of modified Davalos to include a control system and memory, the control system in electrical communication with the memory, the electrochemical sensor, the electrodes and the power supply, the control system configured to execute instructions stored within the memory to cause the control system to detect the detectable signal produced from the one or more analytes passing through the pore of the electrochemical sensor, as taught by Peng, since Peng teaches this configuration would be beneficial for testing and analysis [Para. 0047 of Peng]. Furthermore, the claimed limitations are obvious because all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results, MPEP 2143[I][A].
Modified Davalos and Peng are silent to output a metric indicative of the one or more analytes based on the detectable signal. However, Peng teaches the ionic current [detectable signal] measured by the ammeter is used to characterize the molecules/analyte in the nanopore since the analyte in the nanopore changes/affects the ionic current [Para. 0023 of Peng].
Zhu teaches a nanodevice with a nanopore and electrodes for performing sequencing [Abstract and Para. 0005]. Zhu further teaches a control system 500 [computer] that is configured to output a metric indicative of the one or more analytes [the computer determines the identification of the analyte] based on the detectable signal [the electrical current signature], Para. 0047-0048 and 0058-0059; Figure 4B and 5.
Modified Davalos and Zhu are considered analogous art to the claimed invention because they are in the same field of microfluidic and nanofluidic devices with electrodes for sensing analytes. It would have been obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to modify the control system of modified Davalos to output a metric indicative of the one or more analytes based on the detectable signal as taught by Zhu, since Zhu teaches this would enable identification of the analyte [Para. 0047-0048 and 0058-0059 of Zhu]. Furthermore, the claimed limitations are obvious because all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results, MPEP 2143[I][A].
Regarding claim 15, the system of claim 14, wherein the metric indicative of the one or more analytes includes identification of the analyte, size, charge, charge distribution, charge polarity, conformation, monomer sequence in a polymer, polymer branching, particle coating, conformational stability, pKa, shape, passage time through the pore, mobility, interaction with the pore or other species in solution, or combinations thereof (Modified Davalos as applied to claim 14 above teaches the metric indicative of the one or more analytes includes identification of the analyte [Para. 0047-0048 and 0058-0059 of Zhu].
Regarding claim 16, the system of claim 14, the limitation “wherein the detectable signal includes a resistive pulse indicative of the one or more analytes bouncing against the pore” is a functional recitation. Apparatus claims cover what a device is, not what a device does [MPEP 2114(II)]. A functional recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. See MPEP 2114. In the instant case, modified Davalos as applied to claim 14 above teaches the system that is specifically configured to produce the detectable signal which includes a resistive pulse indicative of the one or more analytes bouncing against the pore (Modified Davalos teaches a nanopore where a detectable signal includes an ionic current where the molecule in the nanopore changes/affects the ionic current [Para. 0023 of Peng]. The detectable signal thus includes a resistive pulse indicative of the one or more analytes bouncing against the pore, as the measured ionic current as the analyte passes through the pore would be related to the resistance of the ionic buffer in the nanopore [Para. 0031 of Peng], and thus meets the claimed limitation).
Claim(s) 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Davalos in view of Peng, Ding, Zenhausern, and Zhu as applied to claim 16 above, and further in view of Chuah et al. (Nanopore blockade sensors for ultrasensitive detection of proteins in complex biological samples, 2019, Nature Communications, 10, Pages 1-9).
Regarding claim 17, modified Davalos is silent to wherein the pore includes a functional group that binds the one or more analytes.
Chuah teaches a nanopore sensor for detecting individual species passing through a nanoscale pore (Abstract and Figure 1). Chuah further teaches the nanopore includes a functional group of an antibody [which is a protein] coupled to the surface of the nanopore by chemical modification that binds a specific analyte (Abstract, Figure 1a, Page 8, Col. 1, Para. 1-2 and Page 2, Col. 2, Para. 1). The antibody functionalized nanopore is beneficial for capturing analytes and improving analyte specificity in nanopore sensors [Abstract and Page 2, Col. 2, Para. 1].
Modified Davalos and Chuah are considered analogous art to the claimed invention because they are in the same field of biological sensors. It would have been obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to modify the nanopore of modified Davalos to include an antibody functional group functionalized/coupled that binds one or more analytes, as taught by Chuah, since Chuah teaches this would be beneficial for capturing analytes and improving analyte specificity in nanopore sensors [Abstract and Page 2, Col. 2, Para. 1 of Chuah]. Furthermore, the claimed limitations are obvious because all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results, MPEP 2143[I][A].
The limitation “and wherein the detectable signal is indicative of a captured analyte within the pore” is a functional recitation. Apparatus claims cover what a device is, not what a device does [MPEP 2114(II)]. A functional recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. See MPEP 2114. In the instant case, modified Davalos as applied to claim 16 above teaches the system that is specifically configured to produce the detectable signal that is indicative of a captured analyte within the pore (Modified Davalos teaches a nanopore where a detectable signal includes an ionic current where the molecule in the nanopore changes/affects the ionic current [Para. 0023 of Peng]. The modification as outlined above yields a nanopore that includes a functional group [an antibody] that binds an analyte and thus the detectable signal would be indicative of a captured analyte within the nanopore [Chuah: Abstract, Figure 1a, Page 8, Col. 1, Para. 1-2 and Page 2, Col. 2, Para. 1]).
Claim(s) 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Davalos et al. (US-20080105565-A1) in view of Peng et al. (US-20140027287-A1).
Regarding claim 21, a system comprising: an insulator-based dielectrophoresis device (Davalos teaches a system comprising an insulator-based dielectrophoresis device [iDEP], Para. 0003) comprising
(i) a fluid flow channel defined by a first substrate surface and a second substrate surface spaced from the first substrate surface (Davalos teaches a fluid flow channel 101 defined by a first substrate surface and a second substrate surface spaced from the first substrate surface [opposing surfaces/walls in a channel which are spaced apart from each other], Para. 0014 and Figure 1. The opposing surfaces/walls in a channel meet the limitation of a first substrate surface and a second substrate surface as evidenced by the instant specification which recites the first and second substrate surface 22, 24 may be formed on the same substrate 11 (e.g., opposing surfaces in a channel) [Para. 0034 of the instant specification]), the fluid flow channel having at least one fluid inlet and at least one fluid outlet (Davalos teaches the fluid flow channel 101 has at least one fluid inlet 103a and at least one fluid outlet 104, Figure 1 and Para. 0053),
(ii) at least one insulating flow structure extending from the first substrate surface toward the second substrate surface thereby defining a constriction in the fluid flow channel between the first substrate surface and the second substrate surface (Davalos teaches at least one insulating flow structure 105a extending from the first substrate surface toward the second substrate surface [the insulating structure is on or in at least one wall of the microchannel and thus extends from the first substrate surface/microchannel wall toward the second substrate surface/opposing microchannel wall], thereby defining a constriction [the area/spaces between the insulating structures 105a] in the fluid flow channel 101 between the first substrate surface/microchannel wall and the second substrate surface/opposing microchannel wall, Figure 1 and Para. 0014, 0038, and 0041);
electrodes in electrical communication with the at least one fluid inlet and the at least one fluid outlet of the fluid flow channel (Davalos teaches electrodes in electrical communication with the at least one fluid inlet 103a and the at least one fluid outlet 104 of the fluid flow channel 101 [the electrode connected to microchannel inlet 103a is connected to a positive voltage terminal and the electrode connected to microchannel outlet 104 is electrically grounded], Figure 1 and Para. 0053), the limitation “wherein the electrodes are positioned to generate a spatially non-uniform electric field across the at least one insulating flow structure of the fluid flow channel to exert a dielectrophoretic force on the one or more analytes suspended in the fluid within the fluid flow channel” is a functional recitation. Apparatus claims cover what a device is, not what a device does [MPEP 2114(II)]. A functional recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. See MPEP 2114. In the instant case, Davalos teaches the above electrodes that are specifically configured to perform the functional limitations above (Davalos teaches the electrodes are positioned to generate a spatially non-uniform electric field across the insulating flow structure 105a of the fluid flow channel 101, since the electrodes provide an electric field and the electric field is made non-uniform by the insulating structures on or in the wall of the microchannel, Para. 0038 and 0042. This exerts a dielectrophoretic force on the one or more analytes suspended in the fluid within the fluid flow channel 101 in which different species of analytes can be by separated or concentrated using iDEP, Para. 0035-0036, 0038, 0042, 0045, and 0076);
a power supply connected to each of the electrodes to generate an electric field within the fluid flow channel (Davalos teaches a power supply connected to each of the electrodes at the microchannel inlets 103a and 104 to supply a voltage [corresponding to an electric field] to electrodes for iDEP within the fluid flow channel 101, and thus generates an electric field within the fluid flow channel, Para. 0076-0077 and 0071, Figure 1; Fig.7 shows an AC power source [Para. 0080]), and
a detection chamber placed in fluid communication with the fluid flow channel by an opening in either the first substrate surface or the second substrate surface, wherein the opening is configured downstream of the at least one insulating flow structure (Davalos teaches a detection area 109 and the area after 106 to port 108 including detection area 109 corresponding to the detection chamber [concentrated analytes move through area 106 to port 108 through a detection area 109, Para. 0054 and see annotated Fig. 1 of Davalos above] placed in fluid communication with the fluid flow channel 101 by an opening in either the first substrate surface/wall or the second substrate surface/wall, wherein the opening is configured downstream [on the right of] the at least one insulating flow structure 105a, Figure 1 and Para. 0054), wherein the detection chamber includes an electrochemical sensor (Davalos teaches the detection chamber [the area after area 106 to port 108, see annotated Fig. 1 of Davalos above] includes an electrochemical sensor, which is the area after 106 to detection area 109 with sensing electrodes 110a and 110b [see annotated Fig. 1 of Davalos above]), the limitation “configured to constrict a flow of a fluid entering the detection chamber” is a functional recitation. Apparatus claims cover what a device is, not what a device does [MPEP 2114(II)]. A functional recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. See MPEP 2114. In the instant case, Davalos teaches the above electrochemical sensor as seen in annotated Fig. 1 that is specifically configured to perform the functional limitations above (Davalos teaches the electrochemical sensor which is the area after 106 to 109 with sensing electrodes 110a and 110b configured to constrict the flow of fluid entering the detection chamber [the area after area 106 to port 108], since the area after 106 to detection area 109 is constricted/much smaller than the channel 101, it is configured to constrict the flow of fluid entering the detection chamber [the area after area 106 to port 108], see annotated Figure 1 above and Para. 0054)
Davalos is silent to through a pore, wherein the pore is sized to produce a detectable signal upon passage of one or more analytes through the pore; wherein the pore is a nanopore. However, Davalos teaches a detectable signal [impedance] is produced upon passage of one or more analytes through the detection area 109 (Para. 0054 and Figure 1).
Peng teaches a device where the capture rate of molecules in a nanopore is increased via dielectrophoresis [Para. 0002]. Peng further teaches an electrochemical sensor/device 101 configured to constrict the flow of fluid entering the detection chamber/fluidic cell 114 through a nanopore 103 and the nanopore 103 separates a first chamber [microfluidic channel 102 from a second chamber [fluidic channel 114] (Para. 0023, 0038 and Figures 1-2). Additionally, Peng teaches the nanopore is sized [nm size] to produce a detectable signal [a measured ionic current] upon passage of one or more analytes/molecules 119 through the nanopore 103, where the molecule 119 changes/affects the ionic current, Para. 0023 and Figures 1-2. This configuration is beneficial since it allows for characterizing the molecule 119 while in the nanopore and can be used for sequencing biological samples, such as DNA [Para. 0023 and 0014].
Davalos and Peng are considered analogous art to the claimed invention, because they are in the same field of microfluidic devices using dielectrophoresis [see e.g., Para. 0002 of Peng and Abstract of Davalos]. It would have been obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to modify the detection area and electrochemical sensor of Davalos to include a nanopore where the flow of fluid is constricted upon entering the detection chamber through a pore and which is sized to produce a detectable signal upon passage of one or more analytes through the pore, wherein the pore is a nanopore, as taught by Peng, since Peng teaches this configuration would be beneficial for characterizing an analyte/molecule while in the nanopore and for sequencing biological samples, such as DNA [Para. 0023 and 0014 of Peng]. Furthermore, the claimed limitations are obvious because all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results, MPEP 2143[I][A].
an additional electrode positioned in the detection chamber (Davalos teaches an additional electrode positioned in port 108 [Paras. 0053-0054 of Davalos], and thus the electrode is positioned in the detection chamber which includes the area after 106 to port 108 as outlined in the rejection above [see annotated Fig. 1 of Davalos above, Paras. 0053-0054 of Davalos]),
the limitation “the additional electrode biasing the spatially non-uniform electric field between the additional electrode and one of the electrodes in electrical communication with the at least one fluid inlet or biasing the spatially non-uniform electric field between the additional electrode and another of the electrodes in electrical communication with the at least one fluid outlet of the fluid flow channel” is a functional recitation. Apparatus claims cover what a device is, not what a device does [MPEP 2114(II)]. A functional recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. See MPEP 2114. In the instant case, Davalos teaches the above additional electrode positioned in port 108 and the detection chamber as seen in annotated Fig. 1 that is specifically configured to perform the functional limitations above (Davalos teaches the electrode at port 108 are allowed to float, and to divert the concentrated analytes through the detection area 109, the voltage at the inlet 104 is raised, then the voltage at port 108 is changed from floating to ground, thereby causing the concentrated analytes to move through area 106 to port 108 through a detection area 109 [Paras. 0053-0054 of Davalos]. Davalos further teaches the voltage at the electrode in the microfluidic inlet 103a was set to a threshold level (Vth), while the electrode at port 108 was set to ground [Para. 0078 of Davalos]. Thus, the electrode at port 108 [the additional electrode in the detection chamber] biases the spatially non-uniform electric field by applying a voltage between the additional electrode and one of the electrodes in electrical communication with the at least one fluid inlet [the electrode in the microfluidic inlet 103a] across the insulating flow structure 105a, since the electrodes provide an electric field and the electric field is made non-uniform by the insulating structures on or in the wall of the microchannel. Additionally, different non-uniform electric fields may also be induced by application of different electrical currents [Para. 0045]. Therefore, the electrode at port 108 [the additional electrode in the detection chamber] is capable of and specifically configured to perform the functional limitations above [Para. 0035-0036, 0038, 0042, 0045, 0053-0054, 0078 and 0076 of Davalos]).
Response to Arguments
Applicant's arguments, see Remarks Pgs. 8-13, filed 03/28/2025, with respect to the 35 U.S.C. § 103 rejections have been fully considered and are not persuasive.
Applicant’s Argument #1:
Applicant argues on page 9 that Davalos, Peng, Ding, and Zenhausern do not teach or suggest an additional electrode positioned in the detection chamber, the additional electrode biasing the spatially non-uniform electric field between the additional electrode and one of the electrodes in electrical communication with the at least one fluid inlet or biasing the spatially non-uniform electric field between the additional electrode and another of the electrodes in electrical communication with the at least one fluid outlet of the fluid flow channel as recited in amended independent claim 1. Therefore, it is submitted that the rejection of independent claim 1 (and claims 2-3, 6-7, 10-13, and 18 that depend thereon) under 35 U.S.C. §103 using Davalos, Peng, Ding, and Zenhausern does not apply to independent claim 1.
Applicant further argues on pages 9-10 that Liu does not make up for the deficiencies of Davalos, Peng, Ding, and Zenhausern detailed above. Therefore, it is submitted that the rejection of dependent claims 4-5 (which depend from independent claim 1) under 35 U.S.C. §103 using Davalos, Peng, Ding, does not apply to independent claim 1.
Applicant further argues on pages 10-11 that Chuah does not make up for the deficiencies of Davalos, Peng, Ding, and Zenhausern detailed above. Therefore, it is submitted that the rejection of dependent claims 8-9 (which depend from independent claim 1) under 35 U.S.C. §103 using Davalos, Peng, Ding, Zenhausern, and Chuah does not apply to independent claim 1.
Applicant further argues on page 11 that Zhu does not make up for the deficiencies of Davalos, Peng, Ding, and Zenhausern detailed above. Therefore, it is submitted that the rejection of dependent claims 14-16 (which depend from independent claim 1) under 35 U.S.C. §103 using Davalos, Peng, Ding, Zenhausern, and Zhu does not apply to independent claim 1.
Applicant further argues on pages 11-12 that Chuah does not make up for the deficiencies of Davalos, Peng, Ding, and Zenhausern detailed above. Therefore, it is submitted that the rejection of dependent claim 17 (which depends from independent claim 1) under 35 U.S.C. §103 using Davalos, Peng, Ding, Zenhausern, Zhu, and Chuah does not apply to independent claim 1.
Examiner’s Response #1:
The examiner respectfully disagrees. As outlined in the rejection of independent claims 1 and 21 above, Davalos teaches an additional electrode positioned in port 108 [Paras. 0053-0054 of Davalos], and thus the electrode is positioned in the detection chamber which includes the area after 106 to port 108 as outlined in the rejection above [see annotated Fig. 1 of Davalos above, Paras. 0053-0054 of Davalos].
In response to applicant's argument that the amended claim includes the additional electrode biasing the spatially non-uniform electric field between the additional electrode and one of the electrodes in electrical communication with the at least one fluid inlet or biasing the spatially non-uniform electric field between the additional electrode and another of the electrodes in electrical communication with the at least one fluid outlet of the fluid flow channel, a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. These arguments are unpersuasive because Modified Davalos teaches all structural limitations as presently claimed device and thus anticipate the claims or render the claims obvious in view of other cited references. The distinctions as argued by applicant are for intended use, e.g., biasing the spatially non-uniform electric field between the additional electrode and one of the electrodes in electrical communication with the at least one fluid inlet, which do not add patentable weight to the presently claimed device.
In the instant case, Davalos teaches the above additional electrode positioned in port 108 and the detection chamber as seen in annotated Fig. 1 that is specifically configured to perform the functional limitations above (Davalos teaches the electrode at port 108 are allowed to float, and to divert the concentrated analytes through the detection area 109, the voltage at the inlet 104 is raised, then the voltage at port 108 is changed from floating to ground, thereby causing the concentrated analytes to move through area 106 to port 108 through a detection area 109 [Paras. 0053-0054 of Davalos]. Davalos further teaches the voltage at the electrode in the microfluidic inlet 103a was set to a threshold level (Vth), while the electrode at port 108 was set to ground [Para. 0078 of Davalos]. Thus, the electrode at port 108 [the additional electrode in the detection chamber] biases the spatially non-uniform electric field by applying a voltage between the additional electrode and one of the electrodes in electrical communication with the at least one fluid inlet [the electrode in the microfluidic inlet 103a] across the insulating flow structure 105a, since the electrodes provide an electric field and the electric field is made non-uniform by the insulating structures on or in the wall of the microchannel. Additionally, different non-uniform electric fields may also be induced by application of different electrical currents [Para. 0045]. Therefore, the electrode at port 108 [the additional electrode in the detection chamber] is capable of and specifically configured to perform the functional limitations above [Para. 0035-0036, 0038, 0042, 0045, 0053-0054, 0078 and 0076 of Davalos]).
Therefore the rejection is maintained.
Applicant’s Argument #2:
Applicant argues on pages 12-13 that Davalos and Peng do not teach or suggest an additional electrode positioned in the detection chamber, the additional electrode biasing the spatially non-uniform electric field between the additional electrode and one of the electrodes in electrical communication with the at least one fluid inlet or biasing the spatially non-uniform electric field between the additional electrode and another of the electrodes in electrical communication with the at least one fluid outlet of the fluid flow channel as recited in amended independent claim 21. Therefore, it is submitted that the rejection of independent claim 21 under 35 U.S.C. §103 using Davalos and Peng does not apply to independent claim 21.
Examiner’s Response #2:
Applicant’s arguments have been fully considered. Based on the Examiner’s Response #1 above, the amended claim 21 is still unpatentable over the prior art of the record. Therefore, the rejection is maintained.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Segawa et al. (US 20060063183 A1) teaches a detecting unit with an opening 21 and means for sequentially moving by dielectrophoresis the target introduced to the detection site [see e.g., Fig. 7B and Abstract]. Paik et al. (US20210048426A1) teaches a sensor including a pore and an applied electric field that is capable of detecting analytes, the sensor including electrodes 0101 on the left- and right-hand side, embedded in a pore 0104 disposed on a substrate 0102 with additional bias electrodes 0103 at the top and bottom [see e.g., Para. 0070, Fig. 1A and Abstract].
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SOMMER OSMAN whose telephone number is (703)756-4790. The examiner can normally be reached Monday-Friday 8:30 - 5:00 EST.
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, James Lin can be reached at (571) 272-8902. 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.
/S.Y.O./Examiner, Art Unit 1794
/SHIZHI QIAN/Primary Examiner, Art Unit 1795