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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 12/30/2025 has been entered.
Response to Amendment
Regarding the amendment filed 12/30/2025: Claims 1-22 and 25-31 are pending.
Response to Arguments
Rejection Under 35 USC 103
Applicant's arguments regarding the rejection of claims 1-22 and 25-30 are rejected under 35 U.S.C. 103 as being unpatentable over Lobdill (US 2017/0082600 A1, cited in IDS heretofore referred to as Lobdill) in view of in view of Klemic et al (US 2004/0168912 A1, heretofore referred to as Klemic) have been fully considered and are not persuasive.
Regarding claims 1, 11, 21, and 22, Applicant argues: “Lobdill describes patch-clamp amplifiers that may be readily manufactured by implementing some or all of the compensation and other circuits using digital circuitry. These digital circuits may be implemented using discrete or integrated logic circuits, programmable logic such as field-programmable gate arrays or programmable logic arrays, or other fixed or configurable logic circuits or combination thereof. Such programmable logic circuits may be reconfigured by a user or by a manufacturer through firmware or software updates when a product update is desired. These circuits may also be quickly reconfigured to allow rapid switching between modes during use. (See Lobdill, Abstract).
Klemic describes ionic electrodes (microelectrodes and electrode arrays), and fabrication methods for such electrodes. Planar polymer electrodes are described in Klemic for making patch clamp measurements of ionic currents through biological membranes, such as the plasma membranes of living cells. The electrodes are described in Klemic as being useful for measuring individual and multisite cell membrane currents and voltages, as well as in high-throughput screening procedures. (See Klemic, Abstract).
Independent claim 1, as amended herein above, relates to an integrated electrophysiology amplifying system, which comprises, inter alia:
a pipette interface configured to receive a device which is a pipette or a sharp
microelectrode; and
an integrated circuit comprising (i) an amplifier coupled to the pipette interface and configured to control a current through the pipette or record a cell membrane voltage, and (ii) at least one compensation circuit which is operated
using a negative feedback,
wherein the integrated circuit and an entirety of the pipette interface are
physically integrated within a common housing.
Independent claim 11, as amended herein above, relates to an integrated electrophysiology amplifying system, which comprises, inter alia:
a pipette interface for receiving a pipette or a sharp microelectrode; and
an integrated circuit comprising (i) an amplifier coupled to the pipette interface and configured to control a cell membrane voltage or record a trans-membrane current, and (ii) at least one compensation circuit which is operated using a
negative feedback,
wherein the integrated circuit and an entirety of the pipette interface are
physically integrated within a common housing.
Amended independent claims 21 and 22 relate to methods, respectively, which recite substantially similar subject matter of amended independent claims 1 and 11, respectively.
Accordingly, each of independent claims 1, 11, 21 and 22 recites that the integrated circuit and an entirety of the pipette interface are physically integrated within a common housing. It is respectfully asserted that the alleged combination of Lobdill and Klemic fails to teach or suggest such recited subject matter of amended independent claims 1, 11, 21 and 22.
In the most-recent Final Office Action, the Examiner continues to allege that Lobdill describes the integrated circuit and the pipette interface being physically integrated within a common housing. (See Final Office Action, p. 3, Ins. 24-26). In alleged support of this allegation, the Examiner points to para. [0063] of Lobdill as disclosing such subject matter, and again states that such passage of Lobdill that such publication "teaches the amplifying headstage which contains the amplifier and connection to the pipette is in a first box near the pipette, i.e. a common housing)." (Id., p. 5, Ins. 9-10).
This section of Lobdill relied on by the Examiner in the Final Office Action states that:
"... In a specific example, the headstage 310 and converters 320-326 are in a first box or on a first board near the pipette 120 and sample 140, while the FPGA 330 is in a second remote box or on a second remote board, where one or more cables convey the digital information between the two." (Lobdill, para.
[0063]).
Thus, as previously stated in the prior response by Applicants, Lobdill only discloses that the headstage 310 and converters 320-326 are in a first box or on a first board near the pipette 120 and sample 140. Then, Lobdill continues that the Field Programmable Gate Array (FPGA) 330 is provided in a second box that is remote from the first box that is provided near the pipette 120. Finally, the cable convey information between the 1st box and the 2nd box. (See Lobdill, para. [0063], and Fig. 3)
However, there is no disclosure in either para. [0063] or Fig. 3 of Lobdill that the integrated circuit and ...the pipette interface are physically integrated within a common housing, as explicitly recited in independent claims 1, 11, 21 and 22. In fact, Lobdill specifically states that the 1st box (which houses the headstage 310 that the Examiner equates to the recited integrated circuit of amended independent claims 1, 11, 21 and 22) is provided near the pipette, but certainly contains absolutely no disclosure, teaching or suggestion that the pipette interface is provided, much less physically integrated in, the same enclosure as its headstage 310.
Nonetheless, the Examiner purports that "the pipette interface of Lobdill is the ... wire V1 is conducted on, which is at least partially contained within the first box and the integrated circuit of Lobdill is the head stage, which the Applicant agrees is contained within the first box." (Final Office Action, p. 5, Ins. 5-7). Thus, it appears that the Examiner now - for the 1st time - equates the wire exiting the headstage 310 that is connected to the pipette capacitor CP and the pipette resister RS to the pipette interface, as recited in amended independent claims 1, 11, 21 and 22. However, such single wire shown in Figure 3 of Lobdill is not and cannot be equated to any interface whatsoever, much less the pipette interface, as recited in amended independent claims 1, 11, 21 and 22. This is because amended independent claims 1, 11, 21 and 22 all recite "a pipette interface configured to receive a device which is a pipette or a sharp microelectrode." This is certainly not the case for the wire of Lobdill labeled by the Examiner as V1 in the Final Office Action. Such wire of Lobdill is not and cannot be configured to receive the pipette 120. Instead, this wire of Lobdill is merely connected to the pipette 120 via the pipette resister RS.
Further, as the Examiner shall ascertain, independent claims 1, 11, 21 and 22 have ben amended to recite that "the integrated circuit and the entirety of the pipette interface are physically integrated within a common housing." In the Final Office Action, the Examiner admits that the wire of Lobdill exiting the headstage 310 is partially provided in the headstage 310 (which the Examiner equates to the common housing). However, it is without a doubt that this wire of Lobdill is certainly not provided in the headstage 310 in its entirety.
Klemic fails to cure the deficiencies of Lobdill to teach or suggest at least the subject matter recited in amended independent claims 1, 11, 21 and 22, and the Examiner does not contend that it does.
Thus, at least based on the reasons provided herein above, Applicants respectfully assert that amended independent claims 1, 11, 21 and 22 are allowable over the alleged combination of Lobdill and Klemic. Accordingly, the 35 U.S.C. § 103 rejection of these independent claims, should be withdrawn. Because claims 2-10 and 25, claims 12-20 and 26, claim 27 and claim 28 depend from, and therefore include all the limitations of amended independent claims 1, 11, 21 and 22, respectively, it is respectfully asserted that these claims are also allowable over the cited prior art for at least the same reasons stated above with respect to amended independent claims 1, 11, 21 and 22. Further, such dependent claims are believed to be allowable due to the additional recitations provided therein and herein above.
Accordingly, the 35 U.S.C. § 103 rejection of these claims should be withdrawn.
The Examiner still respectfully disagrees, the pipette interface of Lobdill is the connection of the wire V1 is conducted on, which is fully contained within the first box and the integrated circuit of Lobdill is the head stage, which the Applicant agrees is contained within the first box. Therefore Lobdill teaches “wherein the integrated circuit and an entirety of the pipette interface are physically integrated within a common housing (Lobdill; Par 0063; Lobdill teaches the amplifying headstage which contains the amplifier and connection of the wire to the pipette is in a first box near the pipette, i.e. a common housing)”. Applicant appears to be arguing that the FPGA of Lobdill is in a second box, which is true, however, the Examiner is not relying on this circuit for any portion of the rejection. Furthermore, even if that was claimed, the Applicant’s motherboard, which is related to the FPGA of Lobdill, is shown to be placed in a second housing, see Applicant’s Figure 1H, which shows a pipette, a headstage, and a motherboard connected via a cable. Therefore the rejection stands.
Regarding claim 31, Applicant argues: “Newly-added claim 31 depends from amended independent claim 1, and claims 3 and 30 which depend from claim 1. Therefore, it is respectfully asserted that the newly-added claim 31 is allowable for at least the reasons described above with respect to amended independent claim 1. In addition, it is respectfully asserted that the subject matter recited in such new claim 31 is separately patentable over the prior art relied on by the Examiner in the Final Office Action.
Indeed, claim 31 recites that "the current-claim module includes a voltage buffer, and ... the [separate] voltage clamp module includes a transimpedance amplifier." There is absolutely no disclosure in Lobdill that the current-claim module includes a voltage buffer or that the separate voltage clamp module includes a transimpedance amplifier, as recited in claim 31. Klemic does not cure such deficiencies of Lobdill to teach or suggest the subject matter recited in claim 31, as it fails to teach or suggest any such recited subject matter of that claim.
Thus, for at least the same reasons as presented herein above, it is respectfully asserted that the subject matter recited in claim 31 is allowable over the art relied on by the Examiner in the Final Office Action. Applicants respectfully request the Examiner confirm the allowability of new claim 31 in a subsequent communication.”. The Examiner respectfully disagrees, Lobdill teaches that wherein the current-claim module includes a voltage buffer (Lobdill; Fig 18, Element 1710 and Par 0082; Lobdill teaches the voltage is buffered by an amplifier, i.e. a voltage buffer), and wherein the voltage clamp module includes a transimpedance amplifier (Lobdill; Par 0012; Lobdill teaches the patch-clamp using a trans-impedance amplifier)”.
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 1-22 and 25-31 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 written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1, 11, 21, and 22 recites “wherein the integrated circuit and an entirety of the pipette interface are physically integrated within a common housing” The specification specifically states “a pipette interface for receiving a pipette or sharp microelectrode, and an integrated circuit having (i) an amplifier coupled to the pipette interface and configured to control a current through a connected pipette or record a cell membrane voltage, and (ii) at least one compensation circuit using negative feedback. The integrated circuit and pipette interface can be physically integrated within a common housing”, in paragraph [0007], with no mention of it being “an entirety of the pipette interface are physically integrated within a common housing”. Furthermore, in Figure 1H and Paragraph [0056], the specification states: “A connector can be included in order to connect to conventional pipette holders for use in patch experiments (see FIG. 1H)”, speaking towards the fact the pipette may be connected to the common enclosure, but not that the entirety of the interface is enclosed. In fact the Examiner is unsure how said pipette interface would be completely enclosed as there necessarily must be some portion of the connect outside the housing to connect to the pipette as taught by Applicant in Paragraph [0056].
Claims 2-21 are rejected for depending on rejected base claim 1.
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.
Claims 1-22 and 25-31 are rejected under 35 U.S.C. 103 as being unpatentable over Lobdill in view of Klemic.
Regarding claim 1, Lobdill teaches an integrated electrophysiology amplifying system (Lobdill; 310 and Par 0058), comprising: a pipette interface (Lobdill; Fig 3, Element Node at V1 and Par 0059; Lobdill teaches a pipette is attached to the amplifier via the wire V1 is conducted on) configured to receive a device which is a pipette or a sharp microelectrode (Lobdill; Fig 3, Element 120 and Par 0059; Lobdill teaches a pipette is used); and an integrated circuit (Lobdill; Fig 3, Element 310) comprising (i) an amplifier (Lobdill; Fig 3, Element 312) coupled to the pipette interface and configured to control a current through the pipette or record a cell membrane voltage (Lobdill; Par 0025 and Par 0059; Lobdill teaches the current to the pipette is controlled and the voltage is measured), and (ii) at least one compensation circuit (Lobdill; Fig 3, Element 320 and Par 0060; Lobdill teaches controlling the current to the pipette involves a compensation current), wherein the integrated circuit and an entirety of the pipette interface are physically integrated within a common housing (Lobdill; Par 0063; Lobdill teaches the amplifying headstage which contains the amplifier and connection of the wire to the pipette is in a first box near the pipette, i.e. a common housing).
Lobdill does not explicitly teaches the compensation circuit which is operated using a negative feedback.
Klemic teaches the compensation circuit (Klemic; Fig 7, Element A1) which is operated using a negative feedback (Klemic; Par 0078; Klemic teaches a negative feedback resistor arrangement).
Before the effective filing date of the invention it would have been obvious to a person of ordinary skill in the art to use the system of Lobdill with the negative feedback of Klemic in order to allow small current and/or voltage detection (Klemic; Par 0233).
Regarding claim 2, the combination of Lobdill and Klemic teaches the system of claim 1. Lobdill further teaches wherein the amplifier is further configured to control the cell membrane voltage or record a trans-membrane current (Lobdill; Par 0059; Lobdill teaches the voltage V1 may be applied to the cell membrane).
Regarding claim 3, the combination of Lobdill and Klemic teaches the system of claim 2.
Lobdill is silent on wherein the amplifier includes (i) a current-clamp module to control the current through the pipette, and (ii) a voltage-clamp module to control the cell membrane voltage.
Klemic teaches wherein the amplifier includes (i) a current-clamp module to control the current through the pipette (Klemic; Par 0235; Klemic teaches a current clamp circuit may be provided using additional circuitry), and (ii) a voltage-clamp module to control the cell membrane voltage (Klemic; Par 0120; Klemic teaches a voltage clamp circuit is used)
Before the effective filing date of the invention it would have been obvious to a person of ordinary skill in the art to use the system of Lobdill with the voltage and current clamp of Klemic in order to allow higher throughput screening (Klemic; Par 0235).
Regarding claim 4, the combination of Lobdill and Klemic teaches the system of claim 3. Lobdill further teaches wherein the current-clamp and voltage-clamp modules share an input (Lobdill; Par 0059; Lobdill teaches the input to the amplifier is the same and that is used to be a voltage clamp or current clamp depending on the compensation required).
Regarding claim 5, the combination of Lobdill and Klemic teaches the system of claim 1. Lobdill further teaches wherein at least one compensation circuit compensates a series resistance associated with the pipette (Lobdill; Par 0015; Lobdill teaches the series resistance of the pipette is compensated for).
Regarding claim 6, the combination of Lobdill and Klemic teaches the system of claim 5. Klemic further teaches wherein the at least one compensation circuit compensates for the series resistance over a range greater than 100 MO (Klemic; Fig. 7, Element 500MO and Par 0233; Klemic teaches the series resistance compensation may be 500MO-1GO).
Regarding claim 7, the combination of Lobdill and Klemic teaches the system of claim 6. Lobdill further teaches wherein the amount of series resistance compensated is programmed via a digital interface (Lobdill; Par 0016 and 0062; Lobdill teaches a series compensation is calculated and the computer is used as a user interface, i.e. a digital interface).
Regarding claim 8, the combination of Lobdill and Klemic teaches the system of claim 1. Lobdill further teaches wherein at least one compensation circuit compensates for a capacitance associated with the pipette (Lobdill; Par 0018; Lobdill teaches the pipette capacitance is compensated for).
Regarding claim 9, the combination of Lobdill and Klemic teaches the system of claim 8. Sherman further teaches wherein the at least one compensation circuit compensates for the capacitance associated with the pipette over a range greater than 10 pF (Klemic; Fig. 7 and Par 0233; Klemic teaches the capacitance compensation may 10pF or greater).
Regarding claim 10, the combination of Lobdill and Klemic teaches the system of claim 9. Lobdill further teaches wherein an amount of the capacitance compensated by the at least one compensation circuit is programmed via a digital interface (Lobdill; Par 0018 and 0062; Lobdill teaches a pipette capacitance is calculated and the computer is used as a user interface, i.e. a digital interface).
Regarding claim 11, Lobdill teaches an integrated electrophysiology amplifying system (Lobdill; 310 and Par 0058), comprising: a pipette interface (Lobdill; Fig 3, Element Node at V1 and Par 0059; Lobdill teaches a pipette is attached to the amplifier via the wire V1 is conducted on) for receiving a pipette or a sharp microelectrode (Lobdill; Fig 3, Element 120 and Par 0059; Lobdill teaches a pipette is used); and an integrated circuit (Lobdill; Fig 3, Element 310) comprising (i) an amplifier (Lobdill; Fig 3, Element 312) coupled to the pipette interface and configured to control a cell membrane voltage or record a trans-membrane current (Lobdill; Par 0024 and Par 0059; Lobdill teaches the voltage to the pipette is controlled and the current is measured), and (ii) at least one compensation circuit (Lobdill; Fig 3, Element 320 and Par 0060; Lobdill teaches controlling the current to the pipette involves a compensation current), wherein the integrated circuit and an entirety of the pipette interface are physically integrated within a common housing (Lobdill; Par 0063; Lobdill teaches the amplifying headstage which contains the amplifier and connection of the wire to the pipette is in a first box near the pipette, i.e. a common housing).
Lobdill does not explicitly teaches the compensation circuit which is operated using a negative feedback.
Klemic teaches the compensation circuit (Klemic; Fig 7, Element A1) which is operated using a negative feedback (Klemic; Par 0078; Klemic teaches a negative feedback resistor arrangement).
Before the effective filing date of the invention it would have been obvious to a person of ordinary skill in the art to use the system of Lobdill with the negative feedback of Klemic in order to allow small current and/or voltage detection (Klemic; Par 0233).
Regarding claim 12, the combination of Lobdill and Klemic teaches the system of claim 11. Lobdill further teaches wherein the amplifier is further configured to control the cell membrane current or record a trans-membrane voltage (Lobdill; Par 0059; Lobdill teaches the voltage V1 may be applied to the cell membrane).
Regarding claim 13, the combination of Lobdill and Klemic teaches the system of claim 12. Lobdill further teaches wherein the amplifier includes (i) a current-clamp module to control the voltage through the pipette (Lobdill; Par 0024; Lobdill teaches a current clamp may be used to control the current), and (ii) a voltage-clamp module to control the cell membrane voltage (Lobdill; Par 0026 and Par 0059; Lobdill teaches a voltage clamp may be used to control the voltage and the voltage V1 may be applied to the cell membrane).
Regarding claim 14, the combination of Lobdill and Klemic teaches the system of claim 13. Lobdill further teaches wherein the current-clamp module and the voltage-clamp module share an input (Lobdill; Par 0059; Lobdill teaches the input to the amplifier is the same and that is used to be a voltage clamp or current clamp depending on the compensation required).
Regarding claim 15, the combination of Lobdill and Klemic teaches the system of claim 11. Lobdill further teaches wherein at least one compensation circuit compensates a series resistance associated with the pipette (Lobdill; Par 0015; Lobdill teaches the series resistance of the pipette is compensated for).
Regarding claim 16, the combination of Lobdill and Klemic teaches the system of claim 15. Klemic further teaches wherein the at least one compensation circuit compensates for the series resistance over a range greater than 100 MO (Klemic; Fig. 7, Element 500MO and Par 0233; Klemic teaches the series resistance compensation may be 500MO-1GO).
Regarding claim 17, the combination of Lobdill and Klemic teaches the system of claim 16. Lobdill further teaches wherein the amount of series resistance compensated by the at least one compensation circuit is programmed via a digital interface (Lobdill; Par 0016 and 0062; Lobdill teaches a series compensation is calculated and the computer is used as a user interface, i.e. a digital interface).
Regarding claim 18, the combination of Lobdill and Klemic teaches the system of claim 11. Lobdill further teaches wherein at least one compensation circuit compensates for a capacitance associated with the pipette (Lobdill; Par 0018; Lobdill teaches the pipette capacitance is compensated for).
Regarding claim 19, the combination of Lobdill and Klemic teaches the system of claim 18. Klemic further teaches wherein at least one compensation circuit compensates for the capacitance associated with the pipette over a range greater than 10 pF (Klemic; Fig. 7 and Par 0233; Klemic teaches the capacitance compensation may 10pF or greater).
Regarding claim 20, the combination of Lobdill and Klemic teaches the system of claim 19. Lobdill further teaches wherein an amount of the capacitance compensated by the at least one compensation circuit is programmed via a digital interface (Lobdill; Par 0018 and 0062; Lobdill teaches a pipette capacitance is calculated and the computer is used as a user interface, i.e. a digital interface).
Regarding claim 21, Lobdill teaches a method for using or providing an integrated electrophysiology amplifying system (Lobdill; 310 and Par 0058), the method comprising: facilitating a receipt of a device which is a pipette or a sharp microelectrode (Lobdill; Fig 3, Element 120 and Par 0059; Lobdill teaches a pipette is used) using a pipette interface of the system (Lobdill; Fig 3, Element Node at V1 and Par 0059; Lobdill teaches a pipette is attached to the amplifier via the wire V1 is conducted on); and controlling at least one of (i) a cell membrane (Lobdill; Par 0025 and Par 0059; Lobdill teaches the current to the pipette is controlled and the voltage is measured of the membrane), or (ii) a current through the device using an amplifier (Lobdill; Fig 3, Element 312) of an integrated circuit (Lobdill; Fig 3, Element 310) which is coupled to the pipette interface (Lobdill; Fig 3 and Par 0059), wherein the integrated circuit comprises at least one compensation circuit (Lobdill; Fig 3, Element 320 and Par 0060; Lobdill teaches controlling the current to the pipette involves a compensation current), wherein the integrated circuit and an entirety of the pipette interface are physically integrated within a common housing (Lobdill; Par 0063; Lobdill teaches the amplifying headstage which contains the amplifier and connection of the wire to the pipette is in a first box near the pipette, i.e. a common housing).
Lobdill does not explicitly teaches the compensation circuit which is operated using a negative feedback.
Klemic teaches the compensation circuit (Klemic; Fig 7, Element A1) which is operated using a negative feedback (Klemic; Par 0078; Klemic teaches a negative feedback resistor arrangement).
Before the effective filing date of the invention it would have been obvious to a person of ordinary skill in the art to use the system of Lobdill with the negative feedback of Klemic in order to allow small current and/or voltage detection (Klemic; Par 0233).
Regarding claim 22, Lobdill teaches a method for using or providing an integrated electrophysiology amplifying system (Lobdill; 310 and Par 0058), the method comprising: facilitating a receipt of a pipette or a sharp microelectrode (Lobdill; Fig 3, Element 120 and Par 0059; Lobdill teaches a pipette is used) using a pipette interface of the system (Lobdill; Fig 3, Element Node at V1 and Par 0059; Lobdill teaches a pipette is attached to the amplifier via the wire V1 is conducted on); and recording at least one of a cell membrane voltage or a trans-membrane current (Lobdill; Par 0025 and Par 0059; Lobdill teaches the current to the pipette is controlled and the voltage is measured of the membrane) using an amplifier (Lobdill; Fig 3, Element 312) coupled to the pipette interface (Lobdill; Fig 3 and Par 0059), wherein the integrated circuit (Lobdill; Fig 3, Element 310) comprises at least one compensation circuit (Lobdill; Fig 3, Element 320 and Par 0060; Lobdill teaches controlling the current to the pipette involves a compensation current), wherein the integrated circuit and an entirety of the pipette interface are physically integrated within a common housing (Lobdill; Par 0063; Lobdill teaches the amplifying headstage which contains the amplifier and connection of the wire to the pipette is in a first box near the pipette, i.e. a common housing).
Lobdill does not explicitly teaches the compensation circuit which is operated using a negative feedback.
Klemic teaches the compensation circuit (Klemic; Fig 7, Element A1) which is operated using a negative feedback (Klemic; Par 0078; Klemic teaches a negative feedback resistor arrangement).
Before the effective filing date of the invention it would have been obvious to a person of ordinary skill in the art to use the system of Lobdill with the negative feedback of Klemic in order to allow small current and/or voltage detection (Klemic; Par 0233).
Regarding claim 25, the combination of Lobdill and Klemic teaches the system of claim 1.
Lobdill is silent on wherein the at least one compensation circuit includes logic that is entirely situated on a chip of the integrated circuit.
Klemic teaches wherein the at least one compensation circuit includes logic that is entirely situated on a chip of the integrated circuit (Klemic; Fig 7, Fig 10, Par 0078, and Par 0082; Klemic teaches the circuitry is all on a single backplate circuit board).
Before the effective filing date of the invention it would have been obvious to a person of ordinary skill in the art to use the system of Lobdill with the one circuit of Klemic in order to allow reuse of the circuitry for multiple measurement setups (Klemic; Par 0107).
Regarding claim 26, the combination of Lobdill and Klemic teaches the system of claim 11.
Lobdill is silent on wherein the at least one compensation circuit includes logic that is entirely situated on a chip of the integrated circuit.
Klemic teaches wherein the at least one compensation circuit includes logic that is entirely situated on a chip of the integrated circuit (Klemic; Fig 7, Fig 10, Par 0078, and Par 0082; Klemic teaches the circuitry is all on a single backplate circuit board).
Before the effective filing date of the invention it would have been obvious to a person of ordinary skill in the art to use the system of Lobdill with the one circuit of Klemic in order to allow reuse of the circuitry for multiple measurement setups (Klemic; Par 0107).
Regarding claim 27, the combination of Lobdill and Klemic teaches the method of claim 21.
Lobdill is silent on wherein the at least one compensation circuit includes logic that is entirely situated on a chip of the integrated circuit.
Klemic teaches wherein the at least one compensation circuit includes logic that is entirely situated on a chip of the integrated circuit (Klemic; Fig 7, Fig 10, Par 0078, and Par 0082; Klemic teaches the circuitry is all on a single backplate circuit board).
Before the effective filing date of the invention it would have been obvious to a person of ordinary skill in the art to use the system of Lobdill with the one circuit of Klemic in order to allow reuse of the circuitry for multiple measurement setups (Klemic; Par 0107).
Regarding claim 28, the combination of Lobdill and Klemic teaches the method of claim 22.
Lobdill is silent on wherein the at least one compensation circuit includes logic that is entirely situated on a chip of the integrated circuit.
Klemic teaches wherein the at least one compensation circuit includes logic that is entirely situated on a chip of the integrated circuit (Klemic; Fig 7, Fig 10, Par 0078, and Par 0082; Klemic teaches the circuitry is all on a single backplate circuit board).
Before the effective filing date of the invention it would have been obvious to a person of ordinary skill in the art to use the system of Lobdill with the one circuit of Klemic in order to allow reuse of the circuitry for multiple measurement setups (Klemic; Par 0107).
Regarding claim 29, the combination of Lobdill and Klemic teaches the system of claim 1. Klemic further teaches wherein the at least one compensation circuit includes at least one resistance compensation block (Klemic; Par 0235; Klemic teaches a series-resistance compensation may be used) which is operated using the negative feedback (Klemic; Par 0078; Klemic teaches a negative feedback resistor arrangement).
Regarding claim 30, the combination of Lobdill and Klemic teaches the system of claim 3. Klemic further teaches wherein the current-clamp module and the voltage-clamp module are provided separately from one another (Klemic; Par 0120 and Par 0235; Klemic teaches the voltage clamp and the current clamp circuit use separate and additional circuitry for each module).
Regarding claim 31, the combination of Lobdill and Klemic teaches the system of claim 30, wherein the current-claim module includes a voltage buffer (Lobdill; Fig 18, Element 1710 and Par 0082; Lobdill teaches the voltage is buffered by an amplifier, i.e. a voltage buffer), and wherein the voltage clamp module includes a transimpedance amplifier (Lobdill; Par 0012; Lobdill teaches the patch-clamp using a trans-impedance amplifier).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
-Weaver et al teaches an apparatus to measure cell membrane electrical variables.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ADAM S CLARKE whose telephone number is (571)270-3792. The examiner can normally be reached M-F 8am-4pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Huy Phan can be reached on (571)272-7924. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ADAM S CLARKE/Examiner, Art Unit 2858
/JUDY NGUYEN/Supervisory Patent Examiner, Art Unit 2858