DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on December 2, 2025 has been entered.
Response to Amendment
This is an office action in response to applicant’s arguments and remarks filed on December 2, 2025. Claims 1, 3-11, and 13-20 are pending in the application. Claims 11 and 13-20 are withdrawn, and claims 1 and 3-10 are being examined herein.
Status of Objections and Rejections
The objection to the claims from the previous office action is withdrawn in view of Applicant’s amendment.
New objections to the claims are necessitated by the amendments.
All rejections from the previous office action are withdrawn in view of Applicant’s amendment.
New grounds of rejection under 35 U.S.C. 103 are necessitated by the amendments.
Claim Objections
Claim 1 is objected to because of the following informalities:
In line 9, “with ion channels” should read “having ion channels”.
In lines 15-16, “a polarization state of the cell based on the transistor current and state of ion channels of the cell” should read “a polarization state of the cell and a state of the ion channels of the cell”.
Appropriate correction is required.
Claim 3 is objected to because of the following informalities: in line 3, “ion channels” should read “the ion channels”. Appropriate correction is required.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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, 3-5, 7, and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al. (US 2021/0318264 A1) in view of Gupta (US 2018/0333086 A1).
Regarding claim 1, Lee teaches a sensing device (a biosensor, Lee, Fig. 4, para. [0052]), comprising:
a transistor, including an extended gate, source, and drain (an FET element 10 including an extended gate electrode 24, source, and drain, Lee, Figs. 1 & 4, para. [0039], [0053]);
a remote electrode, configured to receive a reference voltage (a reference electrode 22 receiving a reference voltage Vref, Lee, Figs. 1-4, para. [0048], [0050]-[0051], [0053]);
a disposable electrode, coupled between the transistor and the remote electrode, the disposable electrode including a proximal end and a distal end, the proximal end being coupled to the extended gate of the transistor, and the distal end being coupled to the remote electrode (a detachable sensing electrode 26 is connected series between the FET element 10 and the reference electrode 22, one end of the detachable sensing electrode 26 being coupled to the reference electrode 22 to apply the reference voltage Vref to the detachable sensing electrode 26, and the other end of the detachable sensing electrode 26 being coupled to the extended gate electrode 24 of the FET element 10, Lee, Figs. 1-4, para. [0049]-[0051], [0053], [0067]);
wherein the disposable electrode is adapted to load a cell with ion channels and receive a membrane potential of the cell, and the disposable electrode is configured to provide a gate voltage to the extended gate based on a change of the membrane potential and the reference voltage (the detachable sensing electrode 26 is adapted to capture cells having ion channels, and when ions are brought in or out of the cell from the cell membrane, a change in gate voltage Vg is provided to the extended gate electrode 24, Lee, Figs. 1-6, para. [0057]-[0059]; as the reference voltage Vref is applied to the detachable sensing electrode 26, it becomes possible to detect the target from the change in gate voltage Vg provided to the extended gate electrode 24, Lee, Figs. 1-6, para. [0051], [0057], [0059]), and
the transistor is configured to provide different transistor currents at the drain based on a change of the gate voltage (the FET element 10 monitors a change in drain-source currents Ids based on the change in the gate voltage Vg, Lee, Figs. 1-6, para. [0039], [0043], [0057], [0059], [0066]-[0067]).
Lee teaches that the FET element 10 monitors a change in drain-source currents Ids based on the change in the gate voltage Vg in order to monitor the change in the size of the polar capacitor and detect the ions brought in or out of the cells from the cell membrane (Lee, Figs. 1-6, para. [0039], [0043], [0057]-[0059], [0066]-[0067]), and the FET element 10 detects the cells by analyzing a potential change due to adsorption of metabolites due to the drain-source currents Ids change (Lee, Fig. 10, para. [0067]). Lee teaches that the FET element 10 is formed in a body 200 (Lee, Fig. 4, para. [0053]). Lee fails to teach a reading circuit coupled to the transistor; and wherein the reading circuit is configured to determine a polarization state of the cell based on the transistor current and state of ion channels of the cell.
Gupta teaches an extended gate field effect transistor, where the current flowing from the source to drain depends on the gate potential (Gupta, Fig. 9, para. [0053]). Gupta teaches that the potential generated at the surface of the reference electrode can be added to the gate voltage, thus changing the source to drain current flow (Gupta, Fig. 9, para. [0053]). Gupta teaches that such an extended gate field effect transistor can be used in a calcium sensor portion 304, and the source to drain current can be output to the controller 506 as a calcium ion detection signal to be processed (Gupta, Fig. 9, para. [0003], [0053]). Gupta teaches that the controller 506 is disposed in a body portion 302 that is integrally connected with the calcium sensor portion 304 (the extended gate FET) and both are included in an implant 300 (Gupta, Figs. 3 & 5, para. [0028]-[0029]). Gupta teaches that the controller 506 can detect the calcium ion concentration in cells based on the FET current (Gupta, para. [0024], [0035]). Gupta teaches that in muscle cells, opening of voltage gated calcium ion channels across the plasma membrane causes a surge of calcium ion current into the cellular media, which can be detected by the controller 506 (Gupta, para. [0023], [0035]).
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 body 200 of Lee to further include a controller coupled to the FET element for processing the current from the FET element as taught by Gupta in order to yield the predictable result of detecting the concentration of the ions brought in or out of the cells from the cell membrane. 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 limitations “receive a reference voltage,” “disposable,” “load a cell with ion channels and receive a membrane potential of the cell,” “provide a gate voltage to the extended gate based on a change of the membrane potential and the reference voltage,” “provide different transistor currents at the drain based on a change of the gate voltage,” and “determine a polarization state of the cell based on the transistor current and state of ion channels of the cell” are interpreted as intended use and/or functional language. The Courts have held that the manner in which a claimed apparatus is intended to be employed does not differentiate an apparatus claim from the prior art, if the prior art apparatus teaches all of the structural limitations of the claim. See Ex parte Masham, 2 USPQ2d 1647 (BPAI 1987). 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. See MPEP § 2114. The biosensor disclosed by Modified Lee teaches all of the structural limitations of the claim and thus is configured for and capable of performing the intended use and/or functional language as mapped in the rejection supra.
Regarding claim 3, the limitation "the cell comprises cardiomyocytes" is with respect to an article worked upon (cell) and not a positively recited element of the sensing device. Inclusion of the material or article worked upon (cell) by a structure (sensing device) being claimed does not impart patentability to the claims. MPEP § 2115.
Modified Lee teaches wherein the reading circuit is configured to determine the state of ion channels of the cardiomyocytes according to the transistor current (the controller detects the concentration of the ions brought in or out of the cells from the cell membrane based on the current from the FET element 10, Lee, Figs. 1-6, para. [0039], [0043], [0057]-[0059], [0066]-[0067], Gupta, Figs. 5 & 9, para. [0003], [0023]-[0024], [0035], [0053], see modification supra).
The limitation “determine the state of ion channels of the cardiomyocytes according to the transistor current” is interpreted as intended use and/or functional language. The Courts have held that the manner in which a claimed apparatus is intended to be employed does not differentiate an apparatus claim from the prior art, if the prior art apparatus teaches all of the structural limitations of the claim. See Ex parte Masham, 2 USPQ2d 1647 (BPAI 1987). 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. See MPEP § 2114. The biosensor disclosed by Modified Lee teaches all of the structural limitations of the claim and thus is configured for and capable of performing the intended use and/or functional language as mapped in the rejection supra.
Regarding claim 4, Modified Lee teaches wherein the reading circuit and the transistor are disposed in a circuit package (the controller and the FET element 10 are disposed in the body 200, Lee, Fig. 4, para. [0053], Gupta, Figs. 3 & 5, para. [0028]-[0029], see modification supra), and the extended gate is disposed on the boundary of the circuit package (the extended gate electrode 24 is disposed on the boundary of the body 200, Lee, Fig. 4, para. [0053]).
Regarding claim 5, Modified Lee teaches wherein the remote electrode and the disposable electrode are integrally disposed in a replaceable disposable package (the reference electrode 22 and the detachable sensing electrode 26 are integrally disposed in a single use detachable module that can be replaced, Lee, Fig. 4, para. [0053]).
Modified Lee teaches that the reference electrode 22 is made of Ag/AgCl, and the detachable sensing electrode 26 is made of the same material as the extended gate electrode 24 which is indium tin oxide (Lee, Fig. 4, para. [0043], [0048]). Modified Lee fails to teach wherein a material of the remote electrode is the same as the disposable electrode.
However, Lee teaches an alternative embodiment wherein the electrodes can be made of the same material (Lee, para. [0045]). Lee teaches that when the electrodes are made of the same material, the change in the polar capacitor cancels each other, and since the voltage Vg of the gate electrode is always maintained at a constant value, noise due to pH can be removed, so a signal caused by the pH may be canceled to be removed (Lee, para. [0045]).
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 reference electrode 22 and the detachable sensing electrode 26 of Modified Lee to be the made of the same material as taught by another embodiment of Lee because noise due to pH can be removed. Furthermore, the selection of a known material, which is based upon its suitability for the intended use, is within the ambit of one of ordinary skill in the art. MPEP § 2144.07.
The limitations “disposable” and “replaceable disposable” are interpreted as intended use and/or functional language. The Courts have held that the manner in which a claimed apparatus is intended to be employed does not differentiate an apparatus claim from the prior art, if the prior art apparatus teaches all of the structural limitations of the claim. See Ex parte Masham, 2 USPQ2d 1647 (BPAI 1987). 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. See MPEP § 2114. The biosensor disclosed by Modified Lee teaches all of the structural limitations of the claim and thus is configured for and capable of performing the intended use and/or functional language as mapped in the rejection supra.
Regarding claim 7, Modified Lee teaches wherein the remote electrode comprises a first remote electrode and a second remote electrode, the disposable electrode comprises a first disposable electrode and a second disposable electrode (each detachable module comprises a sensing electrode 26 and a reference electrode 22, Lee, Fig. 4, para. [0053], so two detachable modules comprise a first reference electrode 22 and a first sensing electrode 26 on the first detachable module, and a second reference electrode 22 and a second sensing electrode 26 on the second detachable module),
wherein the first remote electrode is coupled to the first disposable electrode, the second remote electrode is coupled to the second disposable electrode (the first reference electrode 22 is coupled to the first sensing electrode 26 on the first detachable module, and the second reference electrode 22 is coupled to the second sensing electrode 26 on the second detachable module, Lee, Fig. 4, para. [0053], [0057] [0067]),
the transistor is switchable and coupled to one of the first disposable electrode or the second disposable electrode (the extended gate electrode 24 of the FET element 10 is coupled to one of the first detachable sensing electrode 26 on the first detachable module or the second detachable sensing electrode 26 on the second detachable module, Lee, Figs. 1-4, para. [0049]-[0051], [0053], [0067]).
The limitations “disposable” and “switchable” are interpreted as intended use and/or functional language. The Courts have held that the manner in which a claimed apparatus is intended to be employed does not differentiate an apparatus claim from the prior art, if the prior art apparatus teaches all of the structural limitations of the claim. See Ex parte Masham, 2 USPQ2d 1647 (BPAI 1987). 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. See MPEP § 2114. The biosensor disclosed by Modified Lee teaches all of the structural limitations of the claim and thus is configured for and capable of performing the intended use and/or functional language as mapped in the rejection supra.
Regarding claim 9, the limitation "the cell is arranged in a reagent, and the reagent further includes a drug acting on the cell" is with respect to an article worked upon (cell, reagent) and not a positively recited element of the sensing device. Inclusion of the material or article worked upon (cell, reagent) by a structure (sensing device) being claimed does not impart patentability to the claims. MPEP § 2115.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Lee in view of Gupta as applied to claim 5 above, and further in view of Chang et al. (US 2021/0239688 A1).
Regarding claim 6, Modified Lee teaches wherein the material of the reference electrode 22 is the same as the detachable sensing electrode 26 which is also the same material as the extended gate electrode 24 (Lee, para. [0045], [0048], see modification supra). Modified Lee fails to teach wherein the material of the remote electrode and the disposable electrode is gold.
Chang teaches a biosensor system package including a transistor structure (Chang, abstract). Chang teaches that a biosensor array 102 includes a plurality of biosensors 103 each functionalized to detect a particular target analyte such as cells (Chang, Figs. 1A-1B, para. [0032]-[0034], [0041]). Chang teaches that a reference electrode 108 provides a reference potential and may be made of Au (Chang, Fig. 1A, para. [0042]). Chang teaches that the biosensor 103 includes a fluid gate 112 having a voltage applied thereto that changes the current Ids between the source and drain electrodes (Chang, Fig. 1B, para. [0043]). Chang teaches that the gate structure includes Au (Chang, para. [0058]).
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 material of the reference electrode 22, the detachable sensing electrode 26, and the extended gate electrode 24 of Modified Lee with Au as taught by Chang in order to yield the predictable result of detecting cells. Simple substitution of one known element for another is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 82 U.S.P.Q.2d 1385 (2007); MPEP § 2143(I)(B). Furthermore, the selection of a known material, which is based upon its suitability for the intended use, is within the ambit of one of ordinary skill in the art. MPEP § 2144.07.
Claims 8 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Lee in view of Gupta as applied to claim 1 above, and further in view of Paulose et al., Development of the EDL-FET Based Cell Culture Platform for Electrical Cell Proliferation Monitoring, ECS Journal of Solid State Science and Technology (2020), 9(12): 121001 (hereinafter “Paulose”).
Regarding claim 8, Modified Lee teaches that the detachable sensing electrode 26 has a receptor antibody fixed thereto that captures cells (Lee, Figs. 4-6, para. [0057]-[0059]). Modified Lee fails to teach wherein the disposable electrode loads the cell with an adhesive layer, the adhesive layer comprising one of fibronectin or gelatin.
Paulose teaches an electrical-double-layer field-effect transistor biosensor system for monitoring of cells (Paulose, abstract). Paulose teaches that gelatin was immobilized on the extended gate and cells were captured over the sensor area and adhered to the gelatin on the extended gate electrodes (Paulose, Fig. 1a, pg. 2, left column, fifth paragraph, pg. 3, left column, second paragraph). Paulose teaches that the immobilization of gelatin and cells causes a significant electrical response in drain current (Paulose, Figs. 2a-2b, pg. 4, left column, first paragraph).
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 receptor antibody of Modified Lee with gelatin as taught by Paulose in order to yield the predictable result of adhering cells to the electrode and causing a significant electrical response in drain current to monitor cells. Simple substitution of one known element for another is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 82 U.S.P.Q.2d 1385 (2007); MPEP § 2143(I)(B). Furthermore , the selection of a known material, which is based upon its suitability for the intended use, is within the ambit of one of ordinary skill in the art. MPEP § 2144.07.
The limitation “loads the cell” is interpreted as intended use and/or functional language. The Courts have held that the manner in which a claimed apparatus is intended to be employed does not differentiate an apparatus claim from the prior art, if the prior art apparatus teaches all of the structural limitations of the claim. See Ex parte Masham, 2 USPQ2d 1647 (BPAI 1987). 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. See MPEP § 2114. The biosensor disclosed by Modified Lee teaches all of the structural limitations of the claim and thus is configured for and capable of performing the intended use and/or functional language as mapped in the rejection supra.
Regarding claim 10, Modified Lee teaches the transistor, the disposable electrode, and the remote electrode (the FET element 10, the detachable sensing electrode 26, and the reference electrode 22 form the biosensor, Lee, Fig. 4, para. [0052]-[0053]). Modified Lee teaches a first potential formed at the interface between the sensing electrode 26 and the solution, and a second potential formed at the interface between the solution and the extended gate electrode 24 (Lee, Fig. 4, para. [0049]). Modified Lee is silent with respect to wherein the transistor, the disposable electrode, and the remote electrode form a stretch-out electrical double layer-gated field effect transistor.
Paulose teaches an electrical-double-layer field-effect transistor (EDL-FET) biosensor system for monitoring of cells (Paulose, Fig. 1a, abstract). Paulose teaches that the EDL-FET biosensor comprises an extended gate with cells incubated thereon, and electrical measurement is carried out by biasing the extended gate electrode and measuring current gain (Paulose, Fig. 1a, pg. 2, right column, third paragraph, pg. 3, left column, last paragraph). Paulose teaches that cell proliferation in the sensor surface was electrically measured as drain current change (Paulose, abstract, pg. 1, left column, fifth paragraph, pg. 5, right column, last paragraph). Paulose teaches that when a positive gate bias is applied to the separated gate electrode, the accumulation of positive and negative charges results in increased electron concentration and conductivity and an electric double layer forms in both the gate electrode and the solution interface (Paulose, pg. 2, left column, fifth paragraph, pg. 3, right column, second paragraph). Paulose teaches that the EDL-FET sensor possesses significant advantages in terms of direct monitoring, signal amplification, long time measurement, and sensor operation (Paulose, pg. 2, left column, first paragraph).
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 biosensor comprising the FET element 10, the detachable sensing electrode 26, and the reference electrode 22 of Modified Lee to form an electrical-double-layer field-effect transistor biosensor as taught by Paulose because it would possess significant advantages in terms of direct monitoring, signal amplification, long time measurement, and sensor operation (Paulose, pg. 2, left column, first paragraph).
Response to Arguments
Applicant’s arguments with respect to claim(s) 1 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Conclusion
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/V.T./ Examiner, Art Unit 1794
/JAMES LIN/ Supervisory Patent Examiner, Art Unit 1794