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 .
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 29 April 2025 and 06 August 2025 were filed. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Response to Arguments
Applicant’s arguments, see Remarks page 8, filed 26 September 2025, with respect to the objections to the drawings have been fully considered and are persuasive in light of the amendments. The objections to the drawings have been withdrawn.
Applicant’s arguments, see Remarks page 9, filed 26 September 2025, with respect to the objections to the claims have been fully considered and are persuasive in light of the amendments. The objections to the claims have has been withdrawn.
Applicant’s arguments, see Remarks page 9, filed 26 September 2025, with respect to the rejections under 112(b) have been fully considered and are persuasive in light of the amendments. The rejections to the claims have has been withdrawn.
Applicant’s arguments, see Remarks page 10, filed 26 September 2025, with respect to the rejections of independent claims 1 and 22 under 35 U.S.C. 102 have been fully considered and are persuasive in light of the amendments to the claims. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Gong Jian et al in view of Bashir et al and further in view of Huff et al.
Applicant’s arguments, see Remarks page 13, filed 26 September 2025, with respect to the rejections of dependent claims 2, 3, 5, 7, 9, 10 – 12, and 15 – 21 under 35 U.S.C. 103 have been fully considered and are persuasive in light of the amendments to the independent claims. However, upon further consideration, a new ground(s) of rejection is made in view of Gong Jian et al in view of Bashir et al and further in view of Huff et al, as well as Shen, Ward, Sterling, or Yang—please see detailed rejections beginning on page 4 of this action.
Regarding applicant’s arguments that Gong Jian’s device does not teach the use of a return electrode, this deficiency is addressed by the inclusion of Bashir et al. Bashir et al was applied in the non-final rejection filed 26 March 2025 as teaching a ground return electrode, and has been applied to the amended claim 1 in the same manner.
Regarding applicant’s arguments that Gong Jian et al in view of Huff does not teach the limitation regarding the area of the hydrophilic region; The initial rejection was made in view of Gong Jian et al in view of Huff et al, with Huff providing evidentiary support that working electrodes within the claimed size range were well-known in the art. Gong Jian et al, [0096], is relied upon to teach the claimed “wherein the first portion of the FETB comprises a hydrophilic surface area sized relative to the droplet such that the one or more electrodes is capable of conducting a droplet operation to remove the droplet from contact with the hydrophilic surface area of the FETB; […] wherein the first portion of the FETB comprises a gate layer; […] and wherein the first portion of the FETB comprises a hydrophilic area of not less than about 0.01 mm2 and not greater than about 0.1mm2.” Gong Jian et al teaches that a hydrophilic area for droplet operations within the claimed range. Huff et al teaches that such a size is appropriate for the FETB electrodes taught by Gong Jian et al.
Status of Claims
Applicant’s amendments to the claims, filed 26 September 2025, have been entered. Applicants remarks filed 26 September 2025 are acknowledged.
Claims 1, 5, 15 – 17, 19, and 22 are in status “Currently Amended.” Claims 2, 3, 7, 9 – 12, 18, 20, and 21 are in status “Previously presented.” Claims 4, 6, 8, 13, 14, and 23 – 28 are in status “Cancelled.”
Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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 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 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.
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.
Claims 1, 7, 10 – 12, 16, and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Gong Jian et al (WO 2020026200 A1) in view of Bashir et al (WO 2015148981 A1) and further in view of Huff et al (US 20180126381 A1).
With regards to claim 1, Gong Jian et al teaches;
The claimed “a digital microfluidics (DMF) device” has been read on the taught ([0069], “In accordance with the present disclosure, the large number of microdroplets having a uniform size can be used to perform droplet digital PCR on a microfluidic chip.”; The apparatus forming microdroplets which can be used to perform droplet digital PCR on a microfluidic chip reads on a digital microfluidic device);
The claimed “one or more electrodes for conducting droplet operations” has been read on the taught (Figure 1a, electrowetting-on- dielectric (EWOD) device 10, electrodes 14; [0003], "FIG. 1 A is a perspective view of a schematic diagram illustrating an EWOD device 10... The EWOD device includes […] an array of electrodes 14."; [0004], "Referring to FIG. 1 A, a liquid droplet 16 disposed on the surface of the insulating layer 13 may be moved along a certain direction by turning off/off control voltages at electrodes below the droplet and at adjacent electrodes."; An array of electrodes 14 reads on one or more electrodes. A droplet 16 which may be moved along a certain direction reads on conducting droplet operations.);
The claimed “a field effect transistor biosensor” has been read on the taught (Figure 5, ISFET 50; [0006], "Embodiments of the present disclosure provides an apparatus, system, and method for […] reading the DNA concentration of the samples by […] measuring the pH value of each sample through integrated ion-sensitive field- effect transistor (ISFET) sensors, thereby calculating the DNA concentration of the droplet."; [0071], "FIG. 5 is a cross-sectional view of an ISFET device 50…"; an ion-sensitive field effect transistor which can measure DNA concentration reads on a field effect transistor biosensor—see specification of instant application, [0019], “For example, a change in pH of the reagent contacting the gate will change this layer resulting in a different gate potential.”);
The claimed “wherein the FETB is disposed relative to the one or more electrodes to contact a droplet that is positionable by the one or more electrodes relative to at least a first portion of the FETB and wherein the first portion of the FETB comprises a hydrophilic surface area of the FETB” has been read on the taught ([0070], “… a droplet containing multiple different DNA targets can be dispensed on a region of a single microfluidic chip, the droplet is then moved by electrowetting to a next region… the next region where the droplet is moved to may include a plurality of hydrophilic regions… Each of the hydrophilic regions may include an ion-sensitive field-effect transistor (ISFET) sensor…”; The droplet moved to a region including an ion-sensitive field effect transistor sensor reads on the FETB being disposed relative to the one or more electrodes to contact a droplet that is positionable by the one or more electrodes relative to at least a first portion of the FETB. The hydrophilic region which includes an ion-sensitive field-effect transistor reads on the first portion of the FETB comprising a hydrophilic surface area of the FETB.);
The claimed “wherein the hydrophilic patch is sized such that the one or more electrodes is capable of conducting a droplet operation to remove the droplet from contact with the hydrophilic surface area” has been read on the taught ([0063], “Within a certain range of a surface area ratio between the hydrophobic regions and hydrophilic regions, and as well as the interfacial tension between a droplet and the environment (oil or air), the droplet can be moved away from the hydrophobic regions...”; [0076], “…the integrated lab-on-a-chip device 60A may also include a control circuit 67 configured to provide control signals to […] the array of EWOD devices, and the waste region 66 for moving the droplet 61, […] and the residual portion of droplet after passing through the array of EWOD devices.” [0096] describes preferable sizes of hydrophilic regions according to the invention of Gong Jian et al.);
Gong Jian et al further teaches wherein the first portion of the FETB comprises a gate layer of the FETB, as read on the taught ([0071], “…the ISFET device 50 has a substrate 52, a source region S and a drain region D formed in the substrate, a dielectric layer 53 on the substrate, and a floating gate G formed within or on the dielectric layer 53.”);
Gong Jian et al additionally teaches a hydrophilic area which includes the range between about 0.01mm2 and about 0.1mm2 ([0096], “In one embodiment, the raised hydrophilic regions and/or the microwells have a square shape with a width or length in the range between 1 nanometer and 100 microns, preferably between 1 micron and 10 microns...”).
However, Gong Jian et al does not explicitly disclose wherein the first portion of the FETB further comprises a return electrode, and a ground reference electrode; and wherein the first portion of the FETB comprises a hydrophilic area of not less than about 0.01mm2 and not greater than about 0.1mm2.
In the analogous art of field effect transistors, Bashir et al teaches;
The claimed wherein the first portion of the FETB further comprises “a return electrode, and a ground reference electrode” has been read on the taught ([014], “… a field effect transistor (FET) and a paired set of reference electrodes in close proximity to the FET with the FET positioned between the paired set of reference electrodes.”; [0148], “To characterize biasing conditions, one electrode is swept while the second electrode of the pair is grounded…”; The second reference electrode which is grounded reads on a grounded reference electrode.).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device including a first portion of an FETB with a reference electrode as taught by Gong Jian et al with the FET including a grounded reference electrode as taught by Bashir et al, in order to deplete charged ions and generate a stable gate voltage (Bashir et al, [014], “At least one of the paired set of reference electrodes is electrically biased relative to the FET or to another reference electrode to electronically remove at least a portion of charged ions from a sensor area adjacent to a sensor of the FET, and thereby deplete charged ions in the sensor area, wherein the electrical biasing generates a stable FET gate voltage.”).
However, Gong Jian et al does not explicitly disclose wherein the first portion of the FETB comprises a hydrophilic area of not less than about 0.01mm2 and not greater than about 0.1mm2.
In the analogous art of digital microfluidics, Huff et al teaches;
“An electrochemical sensor including a working electrode” has been read on the taught ([0455], “Electrochemical analysis is performed by utilizing a working electrode that detects an electrical signal generated by a electroactive species generated by the presence of an analyte in the sample.”);
“Wherein the working electrode can be in a range 50 μm and 2 mm” has been read on the taught ([0458], “The working electrode 313 has a first diameter (A)... The first diameter A may be about 50 μm-1.9 mm... In embodiments, where the working and reference electrodes (and the counter electrode, if present) are in a coplanar configuration, the total area of the electrodes (including any gaps between the electrodes) may be sized to conform to the droplet diameter (see FIG. 31B).” );
According to MPEP 2144.04(IV)(A), changes in size/proportion are not sufficient to distinguish the instant claims over the prior art, so long as the claimed relative dimensions would not perform differently than the prior art device. Given that Gong Jian et al teaches that the hydrophilic area can perform its function when sized between 0.01mm2 and 0.1mm2, and that Huff at al teaches that a working electrode sensor can function when its area is between 0.01mm2 and 0.1mm2, the examiner submits that the instant claim does not distinguish over Gong Jian et al in view of Bashir et al and further in view of Huff et al.
With regards to claim 7, the device of claim 1 is obvious over Gong Jian et al in view of Bashir et al and further in view of Huff et al.
Gong Jian et al and Bashir et al both fail to disclose wherein the first portion of the FETB comprises a hydrophilic area comprising not more than about 10% of a droplet footprint area of the droplet relative to the FETB.
However, Huff et al teaches;
“An electrochemical sensor including a working electrode” has been read on the taught ([0455], “Electrochemical analysis is performed by utilizing a working electrode that detects an electrical signal generated by a electroactive species generated by the presence of an analyte in the sample.”);
“Wherein the working electrode comprises about 10% or less of a droplet footprint area of the droplet relative to the FETB” has been read on the taught ([0458], “The working electrode 313 has a first diameter (A) that is smaller than the droplet 314 which has a second diameter B. The first diameter A may be about 50 μm-1.9 mm. The second diameter B may be about 100 μm-2 mm. Other ratios of the electrode diameter to the droplet diameter may also be used in the chips of the present disclosure. In embodiments, where the working and reference electrodes (and the counter electrode, if present) are in a coplanar configuration, the total area of the electrodes (including any gaps between the electrodes) may be sized to conform to the droplet diameter (see FIG. 31B).” A working electrode smaller than the droplet, which may be 50 μm, and a droplet which may be 2mm reads on the electrode comprising about 10% or less of the droplet footprint area.);
Additionally, Gong Jian et al teaches a hydrophilic area smaller than the first diameter A described above ([0096], “In one embodiment, the raised hydrophilic regions and/or the microwells have a square shape with a width or length in the range between 1 nanometer and 100 microns, preferably between 1 micron and 10 microns...”).
According to MPEP 2144.04(IV)(A), changes in size/proportion are not sufficient to distinguish the instant claims over the prior art, so long as the claimed relative dimensions would not perform differently than the prior art device. Given that Huff at al teaches that a working electrode sensor can function when its area is 10% or less of the droplet footprint area, and Gong Jian et al teaches a hydrophilic region smaller than the electrode described by Huff et al, the examiner submits that the instant claim does not distinguish over Gong Jian et al in view of Bashir et al in view of Huff et al.
With regards to claim 10, the device of claim 1 is obvious over Gong Jian et al in view of Bashir et al and further in view of Huff et al.
Gong Jian et al additionally teaches;
The claimed “a first substrate comprising the one or more electrodes for conducting droplets, and a first hydrophobic layer, wherein the first hydrophobic layer comprises a first droplet operations surface opposite the one or more electrodes” has been read on the taught (Figure 2a, substrate 22, dielectric layer 23, actuation electrodes 24; [0051], "…a first substrate structure may be formed including the substrate 22, the dielectric layer 23, and the actuation electrodes 24 within the dielectric layer 23…. In other embodiments, the surface of the dielectric layer 23 is coated with a thin hydrophobic film having a submicron thickness."; The first substrate structure reads on a first substrate. The actuation electrodes 24 reads on the one or more electrodes for conducting droplets. The dielectric layer 23 coated with a thin hydrophobic film reads on a first hydrophobic layer. Figure 2a shows dielectric layer 23 surrounding the electrodes with a droplet on top of layer 23, which reads on a first droplet operations surface opposite the one or more electrodes.);
The claimed “a second substrate disposed relative to the first substrate and comprising at least one ground reference electrode and a second hydrophobic layer, wherein the second hydrophobic layer comprises a second droplet operations surface opposite the ground reference electrode” has been read on the taught (Figure 2a, substrate 28, common electrode 29; [0051], "A second substrate structure may include a substrate 28 and a common electrode layer 27 on the substrate 28… In some embodiments, the surface of the common electrode 27 is covered by an insulating layer made from a hydrophobic material."; [0058], "…a common electrode 27 may be driven by a ground potential (gnd)…"; The second substrate structure reads on a second substrate. The common electrode layer which may be driven by a ground potential reads on a ground reference electrode. The insulating layer made from a hydrophobic material reads on a second hydrophobic layer. The hydrophobic material covering the common electrode reads on a second droplet operations surface opposite the ground reference electrode. Figure 2a clearly shows that the second substrate is disposed relative to the first substrate.);
The claimed “a droplet operation gap defined between the first droplet operation surface of the first substrate and the second droplet operations surface of the second substrate” has been read on the taught (Figure 2a, spacer 29; [0051], "In other words, the space or air gap between the first substrate structure and the second substrate structure is determined by the height or thickness of the spacer 29. The space or air gap forms a channel for the droplet.").
With regards to claim 11, the device of claim 10 is obvious over Gong Jian et al in view of Bashir et al and further in view of Huff et al.
Gong Jian et al additionally teaches;
The claimed “wherein at least one of the first hydrophobic layer or the second hydrophobic layer comprises an opening through which the first portion of the FETB is contactable by the droplet when positionable by the one or more electrodes relative to the first portion of the FETB” has been read on the taught (Figure 4B, Electrowetting-on-dielectric device (EWOD) 40B, microwells 49; [0065], "the first dielectric layer 43b includes a plurality of grooves (microwells) 49…"; [0067], "The microwells 49 are filled with a hydrophobic material and spaced apart from each other by an interstitial hydrophobic surface 46."; [0130], "In one embodiment, the EWOD regions each may feature […] an array of […] microwells (as shown in FIGS. 4B and 4D). In some embodiments, each of the […] microwells include one or more ISFET for measuring an ion concentration or a pH value of an associated microdroplet."; [0065], "The EWOD 40B also includes an array of electrodes (not shown) embedded within the first dielectric layer… The droplet 26 is moved by the moving electric field across the surface of the first dielectric layer…"; The microwells 49 formed in the first dielectric layer, which are filled with a hydrophobic material and spaced apart by a hydrophobic surface, and which include an ISFET for measuring an ion concentration read on "an opening in the first hydrophobic layer through which the first portion of the FETB is contactable by the droplet." It will be understood by one of ordinary skill in the art that an ISFET such as described by Gong Jian et al requires contact between a sample and a FET's gate region in order to function, further detailed in [0071-0073]. This supports the interpretation that the microwells comprise an opening through which the FETB is contactable. The electrodes which are embedded within the first dielectric layer and the droplet which moves along the first dielectric layer when an electric field is moved read on the droplet being positionable by the one or more electrodes relative to the first portion of the FETB.).
With regards to claim 12, the device of claim 10 is obvious over Gong Jian et al in view of Bashir et al and further in view of Huff et al.
Gong Jian et al additionally teaches;
The claimed “wherein the first substrate comprises the FETB, wherein the second substrate comprises the FETB, or wherein the first substrate comprises a first FETB and the second substrate comprises a second FETB” has been read on the taught (Figure 4B, first dielectric layer 43b, microwell 49; [0065], "the first dielectric layer 43b includes a plurality of grooves (microwells) 49…"; [0130], "In one embodiment, the EWOD regions each may feature […] an array of […] microwells (as shown in FIGS. 4B and 4D). In some embodiments, each of the […] microwells include one or more ISFET for measuring an ion concentration or a pH value of an associated microdroplet."; The first dielectric layer 43b, which includes microwells containing one or more ISFETs reads on the first substrate comprising the FETB.).
With regards to claim 16, the device of claim 10 is obvious over Gong Jian et al in view of Bashir et al and further in view of Huff et al.
Gong Jian et al additionally teaches;
The claimed “wherein the first substrate comprises a routing layer in electrical communication with the one or more electrodes” has been read on the taught ([0061], " The EWOD device includes a substrate […], a dielectric layer on the substrate, and an array of actuation electrodes (and/or common electrodes) within the dielectric layer, the actuations electrodes and the common electrodes are connected to a control circuit through conductive wirings in the routing channels…"; The conductive wirings in the routing channels connected to the actuation electrodes in the dielectric layer on the substrate reads on the "first substrate comprising a routing layer in electrical communication with the one or more electrodes.").
With regards to claim 22, Gong Jian teaches;
The claimed “a method for detecting an analyte in a sample fluid using a digital microfluidics (DMF) device” has been read on the taught ([0079], “FIG. 8 is a simplified flowchart illustrating a method 80 for operating an integrated lab-on-a-chip apparatus according to an embodiment of the present disclosure.”), the method comprising;
The claimed “moving a sample droplet of the sample fluid into contacting engagement with a first portion of a field effect transistor biosensor (FETB) by operation of one or more electrodes” has been read on the taught (Figure 8, step 803; [0079], "At 803, the method may include moving the droplet toward an EWOD device of the array of EWOD devices across the mixing region, where the droplet is partitioned into a plurality of microdroplets whose pH value before or/and after incubation may be determined by an ISFET sensor formed on the EWOD device"; [0002], "A bulk liquid droplet […] can be moved by an array of electrodes disposed on a substrate…");
The claimed “wherein the first portion of the FETB comprises a hydrophilic surface area of the FET” has been read on the taught ([0070], "In some embodiments, the next region where the droplet is moved to may include a plurality of hydrophilic regions… Each of the hydrophilic regions may include an ion-sensitive field-effect transistor (ISFET) sensor…");
The claimed “detecting an analyte in the sample droplet using the FETB” has been read on the taught (Figure 8, step 805; Figure 8 step 805 recites, "Determine an ion concentration or pH value of the microdroplets." An ion concentration reads on detecting an analyte. [0007] confirms that this determination can be done with the FETB, reciting, " A sensor includes an ion sensitive field effect transistor containing an ion sensing film configured to be exposed to a solution containing in a microdroplet and provide a signal associated with a concentration level of the solution of the microdroplet…");
The claimed “manipulating the sample droplet away from the FETB to remove the sample droplet from the contacting engagement with the hydrophilic surface area of the FETB” has been read on the taught (Figure 8, step 807; [0079], " At 807, the method may collect and discard […] the microdroplets in a waste region…").
Gong Jian et al additionally teaches a hydrophilic area which includes the range between about 0.01mm2 and about 0.1mm2 ([0096], “In one embodiment, the raised hydrophilic regions and/or the microwells have a square shape with a width or length in the range between 1 nanometer and 100 microns, preferably between 1 micron and 10 microns...”).
However, Gong Jian et al does not explicitly disclose wherein the first portion of the FETB further comprises a return electrode, and a ground reference electrode; and wherein the first portion of the FETB comprises a hydrophilic area of not less than about 0.01mm2 and not greater than about 0.1mm2.
In the analogous art of field effect transistors, Bashir et al teaches;
The claimed wherein the first portion of the FETB further comprises “a return electrode, and a ground reference electrode” has been read on the taught ([014], “… a field effect transistor (FET) and a paired set of reference electrodes in close proximity to the FET with the FET positioned between the paired set of reference electrodes.”; [0148], “To characterize biasing conditions, one electrode is swept while the second electrode of the pair is grounded…”; The second reference electrode which is grounded reads on a grounded reference electrode.).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device including a first portion of an FETB with a reference electrode as taught by Gong Jian et al with the FET including a grounded reference electrode as taught by Bashir et al, in order to deplete charged ions and generate a stable gate voltage (Bashir et al, [014], “At least one of the paired set of reference electrodes is electrically biased relative to the FET or to another reference electrode to electronically remove at least a portion of charged ions from a sensor area adjacent to a sensor of the FET, and thereby deplete charged ions in the sensor area, wherein the electrical biasing generates a stable FET gate voltage.”).
However, Gong Jian et al does not explicitly disclose wherein the first portion of the FETB comprises a hydrophilic area of not less than about 0.01mm2 and not greater than about 0.1mm2.
In the analogous art of digital microfluidics, Huff et al teaches;
“An electrochemical sensor including a working electrode” has been read on the taught ([0455], “Electrochemical analysis is performed by utilizing a working electrode that detects an electrical signal generated by a electroactive species generated by the presence of an analyte in the sample.”);
“Wherein the working electrode can be in a range 50 μm and 2 mm” has been read on the taught ([0458], “The working electrode 313 has a first diameter (A)... The first diameter A may be about 50 μm-1.9 mm... In embodiments, where the working and reference electrodes (and the counter electrode, if present) are in a coplanar configuration, the total area of the electrodes (including any gaps between the electrodes) may be sized to conform to the droplet diameter (see FIG. 31B).” );
According to MPEP 2144.04(IV)(A), changes in size/proportion are not sufficient to distinguish the instant claims over the prior art, so long as the claimed relative dimensions would not perform differently than the prior art device. Given that Gong Jian et al teaches that the hydrophilic area can perform its function when sized between 0.01mm2 and 0.1mm2, and that Huff at al teaches that a working electrode sensor can function when its area is between 0.01mm2 and 0.1mm2, the examiner submits that the instant claim does not distinguish over Gong Jian et al in view of Bashir et al and further in view of Huff et al.
Claims 2, 3, and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Gong Jian et al (WO 2020026200 A1) in view of Bashir et al (WO 2015148981 A1) in view of Huff et al (US 20180126381 A1), as applied to claim 1, and further in view of Shen et al (US 8637242 B2).
With regards to claim 2, the device of claim 1 is obvious over Gong Jian et al in view of Bashir et al and further in view of Huff et al.
Gong Jian et al additionally teaches;
“Wherein the FETB is surrounded by a hydrophobic layer, and wherein the hydrophobic layer does not extend relative to the first portion of the FETB” has been read on the taught ([0070], “In some embodiments, the next region where the droplet is moved to may include a plurality of hydrophilic regions spaced apart by an interstitial hydrophobic surface… Each of the hydrophilic regions may include an ion-sensitive field-effect transistor (ISFET) sensor…”);
“Wherein the FETB has a first portion and a second portion housing different components, wherein the second portion is not in contact with the droplet” has been read on the taught (Figure 5, droplet 56, dielectric layer 53, substrate 52; [0071], “Referring to FIG. 5, the ISFET device 50 has a substrate 52, a source region S and a drain region D formed in the substrate, a dielectric layer 53 on the substrate, and a floating gate G formed within or on the dielectric layer 53. The ISFET device further includes a sensing membrane 55 on the floating gate G and below a microdroplet 56, and a reference electrode 57 entirely or partially immersed in the microdroplet 56 and spaced apart from the sensing membrane 55.”; Figure 5 shows that substrate 52 is not in contact with droplet 56. Dielectric region 53 reads on a first portion. Substrate 52 reads on a second portion.);
“Wherein the droplet is contained on the hydrophilic surface surrounded by hydrophobic regions” has been read on the taught ([0007], “The electrodes are configured […] to move the droplet across the dielectric layer in a lateral direction while leaving portions of the droplet on the hydrophilic surface region.”; [0008], “…a third region in communication with the second region and comprising a plurality of hydrophilic surface regions spaced apart from each other by the hydrophobic surface.”).
However, Gong Jian et al in view of Bashir et al and further in view of Huff does not explicitly disclose wherein the FETB has a second portion comprising a hydrophobic layer, and wherein the hydrophobic layer does not extend relative to the first portion.
In the analogous art of droplet manipulation apparatuses, Shen et al teaches;
“Wherein a functional electrode for droplet manipulation has a first portion comprising a hydrophilic region, and a second portion comprising a hydrophobic region, and wherein the hydrophobic layer does not extend relative to the first portion” has been read on the taught ([41], “Each electrode extends beyond the hydrophilic regions of the nucleic acid molecules into the hydrophobic regions surrounding the hydrophilic regions.”; The area of the electrode under the hydrophilic region reads on a first portion of the electrode. The area of the electrode extending into the hydrophobic regions reads on a second portion of the electrode.);
“Wherein the hydrophobic layer is disposed between the second portion of the FETB and the droplet when the droplet is in contact with the first portion of the FETB” has been read on the taught ([25], “The border or ring can be in a hydrophobic state while the dynamic hydrophilic patch is in a hydrophilic state and in this way the border can help contain an aqueous droplet at the patch.”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device including an FETB in a hydrophilic region surrounded by a hydrophobic region as taught by Gong Jian et al with the arrangement of hydrophobic and hydrophilic regions such that electrical components extend outside of a hydrophilic region as taught by Shen et al, in order to contain an aqueous droplet over desired components as taught by Shen et al (Shen et al, [25], “The border or ring can be in a hydrophobic state while the dynamic hydrophilic patch is in a hydrophilic state and in this way the border can help contain an aqueous droplet at the patch.”) without requiring a multiple layers of electrical components like that which is disclosed in Gong Jian et al (see Gong Jian et al Figure 5). According to MPEP 2114.04(V)(B), making components integral is prima facie obvious—see In reLarson, 340 F.2d 965, 968, 144 USPQ 347, 349 (CCPA 1965). In this case, the wiring taught by Shen et al can be made integral through one electronics routing layer.
With regards to claim 3, the device of claim 2 is obvious over Gong Jian et al in view of Bashir et al in view of Huff et al and further in view of Shen et al.
Gong Jian et al additionally teaches;
The claimed “wherein the second portion of the FETB comprises a source of the FETB and a drain of the FETB” has been read on the taught (Figure 5, substrate 52, source region S, drain region D; [0071], "Referring to FIG. 5, the ISFET device 50 has a substrate 52, a source region S and a drain region D formed in the substrate…"; Substrate 52 reads on the second portion of the FETB. Source region S reads on the source of the FETB. Drain region D reads on the drain of the FETB. As can be seen in figure 5, substrate 52 is not in contact with microdroplet 56).
With regards to claim 9, the device of claim 1 is obvious over Gong Jian et al in view of Bashir et al and further in view of Huff et al.
However, Gong Jian et al in view of Bashir et al and further in view of Huff et al does not explicitly disclose wherein removal of the droplet comprises removal of at least 95 volume percentage of the droplet from the first portion of the FETB.
In the analogous art of droplet manipulation apparatuses, Shen et al teaches;
“Wherein the droplet is removed from a detection surface including a hydrophilic region in a way that maintains droplet integrity” has been read on the taught ([22], “…the apparatus including a substrate having an array of dynamic pads (e.g. electrowetting control pads) for performing droplet operations, a subset of the array of dynamic pads including a hydrophilic patch…”; [50], “Individual droplets can be discretely delivered and removed from a detection surface using a technique that maintains droplet integrity such as an electrowetting technique.”);
While Shen et al does not positively recite that 95% or more of the droplet volume is removed from the hydrophilic patch, Shen et al does describe in [51] that the discrete removal of droplets allows the droplets to be reused, “One or more droplets can be re-used in multiple cycles of an amplification, synthesis or sequencing reaction.”
Shen et al goes on to recite in [56] that a given droplet can be reused up to 100 times, “Alternatively or additionally, a droplet can be used no more […] 100 times before it is replaced, discarded or modified.” For a droplet to be 100 times, it must leave behind 1% or less of its volume per use.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device as taught by Gong Jian et al in view of Bashir et al and further in view of Huff et al with the removal of the drop as taught by Shen et al, in order to reuse reagents in drops without additional concentrating or purifying steps ([50], “Thus, the reagents in the droplets can be more readily re-used, for example, without having to resort to procedures for concentrating or purifying reagents.”).
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Gong Jian et al (WO 2020026200 A1) in view of Ward et al (US 20110059599 A1).
With regards to claim 5, the device of claim 1 is obvious over Gong Jian et al in view of Bashir et al and further in view of Huff et al.
However, this combination does not explicitly disclose wherein the gate layer comprises a graphene gate comprising carboxyl functional groups that server as analyte capture elements to modulate a gate voltage of the FETB when contacted by the droplet comprising an analyte.
In the analogous art of field effect transistors, Ward et al teaches;
“A field effect transistor” has been read on the taught ([0020], "FIGS. 8A and 8B depict the formation of additional electronic nanocomponents for the formation of a field effect transistor.");
“Wherein the field effect transistor includes a graphene gate” has been read on the taught ([0041], "The structure shown in FIG. 8B could be the basis of a simple graphene inverter (gate electrodes not shown for simplicity), other graphene gates, or any high-density stacked graphene nanoelectronic architecture.");
“Wherein the graphene is functionalized with carboxyl” has been read on the taught ([0022], "In one exemplary embodiment, the graphene fragments are functionalized with functional groups along the edges of the graphene fragments to promote dispersion in a solvent such as a polar or non-polar solvent. Exemplary functional groups include, but are not limited to, […] carboxyl groups…")
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device as taught by Gong Jian et al with the functionalized graphene gate as taught by Ward et al. According to MPEP 2143(I)(C), use of known techniques to improve similar devices in the same way may be prima facie obvious. In the case of the instant application, the prior art of Gong Jian et al in view of Bashir et al and further in view of Huff et al teaches a “base” device including an FET sensor, upon which the claimed functionalized graphene gate can be seen as an improvement. The prior art of Ward et al contains a “comparable” device that has been improved by the use of a graphene transistor gate with carboxyl functional groups. One of ordinary skill in the art could have applied the known “improvement” technique in the same way to the base device, for the predictable result of modifying the chemical properties of the graphene.
The claim language of “carboxyl groups that serve as analyte capture elements to modulate a gate voltage of the FETB when contacted by the droplet comprising an analyte” is functional language that describes the intended use of the device. Accordingly, it has been given the appropriate patentable weight. Please see MPEP 2114(II), and Hewlett-Packard Co. v. Bausch & Lomb Inc., 909 F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990). As the combined reference teaches all of the structural limitations of the apparatus as defined in claim 5, this additional limitation does not define the instant application over the prior art.
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Gong Jian et al (WO 2020026200 A1) in view of Bashir et al (WO 2015148981 A1) in view of Huff et al (US 20180126381 A1), and further in view of Beauchemin (US 10365321 B2).
With regards to claim 15, the device of claim 12 is obvious over Gong Jian et al in view of Bashir et al and further in view of Huff et al.
However, this combination does not explicitly disclose wherein one of the first FETB or the second FETB comprises a measurement sensor and the other of the first FETB or the second FETB comprises a reference sensor.
In the analogous art of chemical sensing devices, Beauchemin teaches;
The claimed “field effect transistor biosensor” has been read on the taught (Column 3, line 29, “The chemical sensors may for example be chemically-sensitive field effect transistors (chemFETs), such as ion-sensitive field effect transistors (ISFETS).”);
The claimed “wherein one of the first FETB or the second FETB comprises a measurement sensor and the other of the first FETB or the second FETB comprises a reference sensor” has been read on the taught (Column 3, line 18, “Sensor arrays described herein include one or more reference sensors and one or more chemical sensors… A reference sensor may for example have the same or similar structure as a chemical sensor, but lack the chemical sensitivity of the chemical sensor.”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device including a field effect transistor biosensor as taught by Gong Jian et al in view of Bashir et al and further in view of Huff et al, with the measurement sensor and reference sensor as taught by Beauchemin, for the benefit of creating a device which can determine whether the measurement sensors are functioning properly and improving the reliability of the results (Beauchemin, Column 3, line 7, “Techniques are described herein for detecting and/or identifying defects associated with chemical sensor arrays, so that the experiments are not conducted using defective devices. […] If not detected, these defective circuits can result in incorrect data being collected when the array is used to conduct an experiment. By testing the array using the techniques described herein, the issues associated with the subsequent use of a defective sensor array can be reduced or eliminated.”).
Regarding the limitation of claim 12 (from which claim 15 depends), “wherein the first substrate comprises a first FETB, and the second substrate comprises a second FETB”, the location of the first vs second field effect transistor biosensors is held to be mere rearrangement of parts. According to MPEP 2144(VI)(C), rearrangement of parts may be prima facie obvious—please see In re Japikse, 181 F.2d 1019, 86 USPQ 70 (CCPA 1950). As the specification of the instant application does not detail any unexpected results occurring due to the placement of the first or second FETB, this limitation does not define claim 15 over the prior art of Gong Jian et al in view of Bashir et al and further in view of Huff et al.
Claims 17 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Gong Jian et al (WO 2020026200 A1) in view of Bashir et al (WO 2015148981 A1) in view of Huff et al (US 20180126381 A1) as applied to claim 16, and further in view of Sterling (US 20030164295 A1).
With regards to claim 17, the device of claim 16 is obvious over Gong Jian et al in view of Bashir et al and further in view of Huff et al.
Gong Jian et al additionally teaches wherein the device includes electrode control circuitry (Figure 1A, control circuit 15; [0003], "The EWOD device also includes an input-output circuit 15 in the substrate and operative to interface with an external control circuit to provide control voltages having time-varying voltage waveforms to the array of electrodes 14."; [0077] discusses electrode arrangements for control circuitry).
However, Gong Jian et al does not explicitly disclose wherein the routing layer comprises an active matrix driver to selectively activate ones of the one or more electrodes.
In the analogous art of microfluidic devices for droplet manipulation, Sterling teaches;
“An active matrix microfluidic platform” has been read on the taught (Abstract, "An active matrix microfluidic platform employs thin film transistor active ("TFT") matrix liquid crystal display technology to manipulate small samples of fluid…"; [0033] clarifies that the platform can manipulate droplets,"…a microfluidic platform 10 for controlling the motion of fluid droplets via electrowetting droplet control physics.");
“An active matrix driver” has been read on the taught ([0045], "…the various subsystems of the microfluidic platform such as a feedback subsystem 86, row driver 28 and column driver 30." The row driver and column driver read on an active matrix driver to selective active one or more electrodes.).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the DMF device which uses electrodes to manipulate droplets as taught by Gong Jian et al with the droplet microfluidic platform which uses electrodes driven by an active matrix driver as taught by Sterling, in order to take advantage of commercially available manufacturing methods and control software ([0033], "Thus, the invention can take advantage of existing active matrix LCD technology including fabrication techniques and animation software including commercially available video generation or editing software to develop a microfluidic platform 10 for controlling the motion of fluid droplets via electrowetting droplet control physics.").
With regards to claim 18, the device of claim 17 is obvious over Gong Jian et al in view of Sterling.
Sterling additionally teaches;
The claimed “wherein the active matrix driver comprises a drive transistor comprising a drive source and a drive gate” has been read on the taught ([0016], "FIG. 6 is an isometric view of the microfluidic structure, illustrating the two-dimensional matrix array of electrodes, the array of transistors electrically coupled to respective ones of the electrodes, and the gate and source lines for driving the transistors."; [0048], “The transistors 114 are electrically coupled to respective ones of the drive electrodes 26 for controlling the same.”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the DMF device which uses electrodes to manipulate droplets of fluid as taught by Gong Jian et al with the microfluidic platform which uses electrodes to manipulate droplets, driven by an active matrix driver as taught by Sterling, in order to take advantage of commercially available manufacturing methods and control software ([0033], "Thus, the invention can take advantage of existing active matrix LCD technology including fabrication techniques and animation software including commercially available video generation or editing software to develop a microfluidic platform 10 for controlling the motion of fluid droplets via electrowetting droplet control physics.").
Claims 19-21 are rejected under 35 U.S.C. 103 as being unpatentable over Gong Jian et al (WO 2020026200 A1) in view of Bashir et al (WO 2015148981 A1) and further in view of Huff et al (US 20180126381 A1) as applied to claims 1 and 10, and further in view of Yang et al (US 20100141280 A1).
With regards to claim 19, the device of claim 10 is obvious over Gong Jian et al in view of Bashir et al and further in view of Huff et al.
However, Gong Jian et al in view of Bashir et al and further in view of Huff et al fails to teach wherein the device comprises a drop-in portion separate from the first substrate or the second substrate and comprising the FETB, wherein the drop-in portion is selectably engageable to dispose the FETB relative to the droplet operations gap to dispose the first portion in contactable relation with a droplet in the droplet operations gap.
In the analogous art of field-effect transistor biosensors, Yang et al teaches;
The claimed “a drop-in portion separate from the first substrate or the second substrate and comprising the FETB” has been read on the taught (Figure 4, biosensor 1; [0047], "On the top of the measurement module 20, an attachment unit 20a is provided to attach/detach the FET biosensor…"; [0052], “Referring to FIG. 4, the attachment unit of the measurement module 20 may include a groove that has substantially the same size as the biosensor 1 to fix the biosensor 1 therein.");
The claimed “wherein the drop-in portion is selectably engageable to dispose the FETB relative to fluidic components” has been read on the taught ([0053], "…a suitable force is applied by a spring or a damper to the biosensor 1 so that the biosensor 1 may adhere closely to the inlet 21 and the outlet 22. Also, when the cover unit 23 is clo