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 .
DETAILED ACTION
Remarks
This Office Action fully acknowledges Applicant’s remarks filed December 2nd, 2025. Claims 1-4, 9, 13-18, and 62-67 are pending. Claims 5-8, 10-12, and 19-61 are canceled.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 2nd, 2025 has been entered.
Request for Information under 37 CFR 1.105
No IDS was filed for this application. The applicant and/or the assignee of this application are required under 37 CFR 1.105 to provide the following information that the examiner has determined is reasonably necessary to the examination of this application (see MPEP §§ 704.10 - 704.13). In response to this requirement, please provide a copy of any related and pertinent information, such as non-patent literature, published application(s) or patent(s) (U.S. or foreign), that was used to assist in the drafting of this application. The applicant is reminded of the duty to disclose information that is material to patentability (see 37 CFR § 1.56). A complete reply to the instant Office action must include a complete reply to this requirement. The time period for reply to this requirement coincides with the time period for reply to the instant Office action.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-4, 9, 13-18, and 62-67 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Applicant’s specification is not enabled for the recited operating first mode in step b) to “controlling a biasing” (and similarly as in cl. 18 to “a biasing of the…”) and independently control functions (i), (ii) given to the configurations of the cited gates as recited in claim 1 (and dependent claims thereof). This is likewise seen with respect to the independently controlled steps to item (b) in providing functionalities (i),(ii) given to the electrodes in the method of claim 18 (and dependents thereof), and further with the controlling configurations provided in newly-added claims 64-67.
The pertinent Wands Factors are described below and related with the above discussion, which further show that the claims lack a proper scope of enablement.
1) Level of ordinary skill in the art – a PhD level in fields as in electrical engineering, biochemistry/biosensing, microfluidics, semiconductor processing, and lab-on-a-chip technology.
2) Nature of the invention – development of biological field effect transistor (BioFET, or as in a meta-nano-channel BioFET (MNC BioFET), however, MNC BioFET is not a term of art and is drawn to Applicant’s own terminology) that controllably operates to manipulate the electric field generated to the transistor’s channel surface to increase the “Debye screening length) and thus increasing the sensitivity of the BioFET as compared to known BioFETs. This controllable operating of the FETs electrodes/gates is to overcome the electrostatics of the electrical double layer at the channel where the ion solution is present.
3) State of the prior art – While FETs (field effect transistors), and including BioFETs (including probes to immobilize bioanalytes) are known in the art, it is also recognized in the art of BioFETs that the Debye screening length is limited, often times insufficiently short, and provides a known problem for a lack of sensitivity for small biomolecule sensing in BioFETs.
Furthermore, overcoming the Debye screening length’s limitations implicit to BioFETs remains a challenge to engineers in the prior art, including with respect to the presence of the electrical double layer (EDL) exerted as a capacitance to the channel at which the ion solution is present.
Notable prior art as it pertains to overcoming Debye screening length limitations is given as follows-
1) Zheng et al. (Overcome Debye length limitations for biomolecule sensing based on field effective transistors; Chinese Journal of Chemistry, 2021, 39, 999-1008.1002/cjoc.202000584).
Therein, Zheng et al. describe the inherent Debye length limitations in BioFETs including with respect to the presence of the electrical double layer (EDL) (p.1001).
Zheng proposes choosing novel semiconductors with special carrier distribution, decorating special polymolecular on the channel, changing the ion concentration of solution or electrical perturbation (p. 1001-, sec. 3.1-3.3, figs. 3-8 for example).
At section 3.3 Zheng discusses overcoming Debye length limitations by way of modulating the device using electronic field that is most akin to Applicant’s sought controlled mode of operation.
Zheng concludes that charge screening (concerning the presence of an electrical double layer as previously discussed) is inevitable in solution and it is impossible to eliminate the charge screening, which results from the charge interaction, and the screening length depends on the solution medium, ions, and temperature. Zheng further discusses that another challenge is that there is no direct technique to characterize this screening distribution, wherein the phenomenon of charge screening exists in the charged interaction and is difficult to describe and analyzer.
Lastly, Zheng discloses that the last challenge may be that influence and modulation of Debye length on the FET configuration is not clear, wherein current research mainly focuses on studying the sensing performance, and a systemic mechanism about the influence of the FET configuration on the Debye length needs to be studied.
Zheng finalizes that it is not a singular area that needs to be employed to achieve optimal performance, but it is a collaborative application of material improvement, aptamer design, and device modulation that is necessary.
2) Nakatsuka et al. (Aptamer-field-effect transistors overcome Debye length limitations for small-molecule sensing; Science. October 19th, 2018; 362(6412): 319-324. Doi 10.1126/science.aao6750.
Nakatsuka discloses detection of analytes with FETs being ligand-specific receptors is fundamentally limited by the shielding created by the electrical double layer (EDL; and given to the “Debye length” limitation).
Nakatsuka discloses detecting small molecules under physiological high ionic-strength conditions by modifying printed ultrathin metal-oxide field-effect transistor arrays with deoxyribonucleotide aptamers selected to bind their targets adaptively.
Nakatsuka provides that field-effect transistors bearing aptameric stem-loop receptors designed to be conformationally flexible close to semiconductor surfaces detect small-molecule targets under physiological conditions overcoming Debye length limitations.
3) Liu et al. (US 2010/0327874).
Liu discloses a circuit-based arrangement including a circuit-based screening channel with an effective width that is not limited by the Debye screening length along a surface of the substrate connected with fluidic reservoirs for electrically analyzing biomoleuclar interactions therein the screening channel. Liu further discloses providing increased sensitivity to the biomolecular interactions by exploiting electro-diffusion ionic current flow in the flow channel(s) (abstract; pars.[0022,0033,0035], figs., for example).
4) Boyanov (US 2019/0041354).
Boyanov discloses biological field effect transitors (BioFETs) wherein it is acknowledged that the Debye screening length in the salt solutions is in the range of about 0.3 to 10nm which limits the sensing zone to a few nanometers outside the surface of the channel and often reduces signal levels to the limit of detectability. Boyanov proposes a work-around to this difficulty is to perform the biological reaction and measurements in two different buffers- high salt and low salt, respectively. However, Boyanov notes that such an approach is not typically suitable for single-molecule sensors where buffer exchange is not possible (pars.[0002,0072]). Boyanov discloses providing trap states in the channel of a transistor to enhance the observed signal output and improves the limit of detection of the device (par.[0074])
4) Breadth of the claims – extremely broad as the claims encompass as an open-ended and general “control a biasing to independently control as in items (i), (ii)” (and likewise with respect to the method of claim 18 and item b) to functionalities (i), (ii)) that is without particular steps thereto and is merely recited by way of the desired functionality/action to be achieved in each of the independent claims 1, and 37.
The arrangements possible for use are also highly broad as they are herein defined by their intended functionality and absent concordant discussion in the specification to the particular programming/control scheme to accomplish the sought functionalities.
The disclosure is absent particular discussion as to what biasing is particularly applied to “control a biasing” to independently control such functionalities (i), (ii).
Further, the prospective “fluid” that influences the surface charge and electric field within the biosensor is also generic and open-ended, and with respect to the method of claim 18, this is likewise seen with the positively provided fluid to the biosensor.
The breadth is also unduly broad as to the manner of achieving the recited functionalities/results herein claim 1 and 18 to the control to functionalities (i) (ii) and the second mode as in cl. 67.
5) The level of predictability/amount of experimentation required – highly unpredictable given the breadth of the claims in combination with a lack of sufficient disclosure to both the physical configuration of the BioFET (or Applicant’s named “MNC BioFET”) as well as the controller-configuration to the BioFET in terms of the sequence of operations (timing, duration, biasing, current/voltage, and to which of the various electrodes at a given place in the sequence) controllably affected to arrive at the recited functionalities/results.
Further, and as seen above from the disclosure of Zheng, screening length (as it relates to the Debye length) depends on the solution medium, ions, and temperature, and further that all of semiconductor material improvement, aptamer design (i.e. receptors in the sensing area), and device modulation (i.e. configuration of the electrodes) are variables to be considered and necessary in order to develop BioFETs that operate as claimed in preventing a top conductive channel, controlling properties of the conductive channel (and itself drawn to a broad list of variables to size, shape, location), controlling the Debye length, and electrostatically decoupling an interface between the sensing region and the fluid from one or more conductive channels, and as related to the double layer (EDL above in the cited prior art) and its decoupling in BioFETs.
Additionally, the vast variables involved, such as in terms of the number and particular orientation across the biosensor to the various decoupling and additional electrodes, as well as the material of construction of the semiconductor, biochemically with the sensing region and its particular receptors and anchors for those receptors involved (all of which influence surface charge, the conductive channel(s)), and in terms of the particular biosensing desired to the particular biomolecular binding targeted alongside the particular carrier fluid affecting conductivity and charge, and electrically in terms of the electrical engineering involved in attaining the concordant sequence of operations to be carried out for a given configuration for a given biosensing application in terms of timing, duration, biasing, applied current/voltage, and with particular connection to particular ones of the decoupling and additional electrodes provides that an undue amount of experimentation is required.
This is coupled by the fact that the nexus between that which has been claimed and that which is known in the prior art is too large and not remedied/bridged by Applicant’s disclosure. Applicant’s disclosure to the recited controlled configurations for the recited functionalities therein is both general and prophetic to a meta-nano-channel BioFET (see pars.[0067-0070,0083-0091]) and absent the particulars that provide for the sought controlled configurations given to the electrodes of the biosensor for their recited functionalities.
6) Working Examples –
The specification is devoid of working examples.
The specification is made up of general discussion to the general architecture of Applicant’s named “MNC BioFET” with general discussion given to the six-gate architecture and biasing of various gates to potentially form a middle conductive channel, and potentially avoiding formation of a top conductive channel, which is both non-specific and not definitively attained (see pars.[0083-0091]; further noting that these “conductive channels” are not physically defined channels within the semi-conductor but are prospectively produced electrical conductance channels; as opposed to Liu above which discloses dimensioning the physical flow channel for the biomolecules to have an effective width that is not limited by the Debye screening length).
There is also discussion to functionalization for label free detection of PSA that speaks to a desired bioassay and not to the particular controlled configuration of electrodes as claimed and at-issue herein (see par.[0093,0099]).
There is also individual discussion to influencing the width of the conductive channel and potential superior sensing at a formed middle conductive channel than the top channel (par.[0104]).
None of these discussions amount to the claimed controlled electrodes configuration as claimed.
Further, the above discussions themselves are limited, general, and prophetic in nature, absent any particular evidence/data to show the individual phenomenon purported.
Figure 1C is drawn to an example of a graph (Screening length vs. Distance from the interface) and accompanying discussion (par.[0065]) that postulates the ability to overcome the Debye length limitation, and the following discussion in pars.[0066-0070]] sets forth to provide a method that overcomes the challenge and decouple the double layer from the conductive channel, but the disclosure therein shows that it is undetermined and vague.
Applicant’s disclosure to the recited configurations of the claims therein is both general and prophetic to a “meta-nano-channel” BioFET comprising six independent gates (see fig. 2A) and absent the particulars that provide for the sought controlled configurations given to the electrodes of the biosensor for their recited functionalities.
The discussion found in pars.[0065-0078] is generalized and provides narrative discussion that the six gate MNC Bio-FET permits the formation of various conductive channels of different sizes, shapes, and locations. However, the disclosure is absent the particular biasing control (i.e. particular voltages applied and to what gate(s) in each instance of (i), (ii)) that affords actual control of the recited one or more properties (i.e akin to the size, shape, location), let alone with respect to independently controlling this aspect (i) alongside (ii) in controlling the Debye length.
Applicant’s disclosure also generally sets forth the methodology akin to claim 18 in pars.[0130-0163], however such disclosure is both general and prophetic and does not amount to a working example providing basis for the controlled configuration of the electrodes as recited throughout the claims (including the devices of the biosensor in 1-17, and 37, and the method of claim 18).
Further, Applicant’s disclosure is devoid of particular examples to the configurations of the electrodes when operating in a first mode that provide to control one or more properties of other conductive channels comprising six independent gates (see fig. 2A and (ii) the Debye length at an interface between the sensing region and the fluid (see pars.[0083-0091]), as well as with a first mode wherein the decoupling electrodes operate in a first mode to electrostatically decouple as claimed. This is additionally seen with the lack of discussion to a particularly-implemented and configured controller/processor affecting the various electrical events in order to provide such mode of operation and independent control as claimed (i.e. the necessary complete circuitry configuration).
Additionally, Applicant’s disclosure further acknowledges the Debye screening length limitation as a fundamental challenge, and provides “…[o]ne straightforward approach to overcome EOI screening length is to bias the reference electrode with respect to substrate in order to achieve bulk Debye length at the EOI. However, biasing at the reference electrode affects also the band bending at the BioFET silicon/gate-dielectric interface and hence the conductive channel” (par.[0090]).
This discussion does not provide a definitive solution, let alone one coincident and commensurate with the claimed controlled configuration of the electrodes as claimed, and in fact, provides that the purported solution to overcoming EOI screening length is not a solution at all as it relatedly affects the conductive channel.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-4, 9, 13-18, and 62-67 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The claims are indefinitely recited for their given configurations to the electrodes.
The amended claims provide that the control unit provides items (a) and (b) involving controlling a biasing of various gates, however, the claims themselves are without voltage sources to respective gates of the bio-FET and being cooperatively coupled with the control unit in order to allow for any sort of control operations to affect a biasing thereof said respective gates.
It is not clear from the specification what configuration(s) of the decoupling/additional electrodes (i.e. their physical, relative arrangement and connection with one another and constituent elements within the FET, as well as the number thereof) and coincident particular-applied control to the current/voltage and with respect to its duration, extent, biasing, and order of operations provide to yield the sought functionalities given in the claims.
Herein, the claimed biosensors and method of use thereof is set forth with desired functionalities (i) and (ii) being independently controlled as in cls. 1 and 18 as a consequence of a controlled biasing thereof the top reference electrode gate, back gate, and lateral gates and controlled operation thereof, however, Applicant’s specification does not particularly discuss or definitively defined such ‘controlled biasing’ that affords the functionalities (i), (ii) and being independently controlled.
Examiner notes discussion of a meta-nano-channel (MNC) BioFET wherein this is not a term of art (BioFET is, however, MNC BioFET is drawn to Applicant’s own terminology. Further, the discussion of such MNC BioFET comprising six independent gates (see fig. 2A) is general and prophetic in nature to the recited functionalities of “prevent formation of a top conductive channel…”, “(i) independently control one or more properties…,” and “(ii) [independently control a Debye length….” (as in cls. 1&18).
Furthermore to this, such modal/independent and controlled operation and a controller’s particular sequencing is not provided (fig. 2A merely shows a control unit schematically-adjacent the MNC BioFET).
Clarification is required.
Claim 3 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 3 recites the limitation "the control circuit”. There is insufficient antecedent basis for this limitation in the claim. Is this an additional element or does Applicant intend to recite “the control unit?”
Response to Arguments
Applicant's arguments filed December 2nd, 2025 have been fully considered but they are not persuasive.
With regards to claims 1-18 and 37 rejected under 35 USC 112a/1st as failing to comply with the enablement requirement, Applicant traverses the rejection.
Applicant generally offers figs. 2B,D-G,J along with general reference to pars.[0053,0058,0065-0078] and general conclusory remarks thereto.
Examiner asserts that this does not provide a persuasive and substantive response to the particular issues at-hand that have been cited previously with respect to the various Wands factors. Further, these cited figures and paragraphs do not provide enabling disclosure to the above-cited enablement issues under 35 USC 112 a/1st, and Applicant has not provided particular discussion thereto so as to provide persuasive and substantive remarks as to purported enabling support provided therein to the claims at-hand.
The discussion found in pars.[0065-0078] is generalized and provides narrative discussion that the six gate MNC Bio-FET permits the formation of various conductive channels of different sizes, shapes, and locations. However, the disclosure is absent the particular biasing control (i.e. particular voltage(s) applied and to what gate(s) in each instance of (i), (ii)) that affords actual control of the recited one or more properties (i.e akin to the size, shape, location), let alone with respect to independently controlling this aspect (i) alongside (ii) in controlling the Debye length.
Concordantly with such a response by Applicant, Examiner asserts that the claims remain rejected under 35 USC 112 a/1st as failing to comply with the enablement requirement for the reasons particularly discussed above in the body of the action and in the prior actions. The rejection herein is afforded to the claims as amended, and which constitutes claims 1-4, 9, 13-18, and 62-67.
The amendments in claims 1 and 18 in item (b) to “control a biasing…” to independently control as in items (i), (ii) (and similar language as in cl. 18 to “biasing the top…back…lateral…to independently control…(i)…(ii)…”) remain inadequately described in the specification, including those sections cited by Applicant, and do not comply with the enablement requirement.
This is likewise seen in newly-added cls. 64-67 in which the recited controlling therein is not described in the specification in such a way as to enable one skilled in the art to make/use the invention and concordant with the inadequate disclosure as it pertains to the control with respect to one or more properties as claimed and the related control of the Debye length at the interface.
With regards to claims 1-18 and 37 rejected under 35 USC 112b/2nd, Applicant traverses the rejection.
Examiner asserts that the rejection has been overcome in-part, however issues of indefiniteness remain.
As discussed above, the metes and bounds of item (b) in both of claims 1 and 18 in the “control a biasing” (and similar language as in cl. 18) to afford the functionalities (i), (ii) is indefinitely defined and not particularly set forth in the specification.
Further, as amended, the claims provide that the control unit provides items (a) and (b) involving controlling a biasing of various gates, however, the claims themselves are without voltage sources to respective gates of the bio-FET and being cooperatively coupled with the control unit in order to allow for control operations to affect a biasing thereof said respective gates.
Claims 1-4, 9, 13-18, and 62-67 remain rejected under 35 USC 112 b/2nd for the reasons discussed above and in the body of the action.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NEIL N TURK whose telephone number is (571)272-8914. The examiner can normally be reached M-F 930-630.
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/NEIL N TURK/Primary Examiner, Art Unit 1798