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 .
Information Disclosure Statement
The information disclosure statement (IDS) was submitted on 01/06/2026. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Response to Arguments
Claims 1-2, 5-7, 10, 13-16,1 8-20, 22, 24-25, 27, 31, 40 and 43-44 are pending.
Claims 4 and 30 are cancelled.
Claims 1, 5, 7, 10, 14, 15, 18-20, 24, 27, 40, and 43 are amended. Amendments have been fully considered and are accepted.
Applicant's arguments filed 01/06/2026 have been fully considered.
Regarding objection to specification under 35 U.S.C. 112(a), objection is withdrawn based on amendments to specification.
Regarding rejection of Claims 10, 20 and 27 under 35 U.S.C. 112(b). Examiner agrees with applicant that amendments to Claims 10, 20, and 27 overcome rejection. Rejections of Claims 10, 20, and 27 are withdrawn.
Regarding rejection of Claims 1-2, 4-7, 10, 13-15, 18-19, 22, 24-25, 27, 30-31, and 43-44 under 35 USC § 103, Applicant’s arguments have been fully considered, but are not persuasive.
With regard to independent Claims 1 and 18, rejected as unpatentable over obvious combination of prior art by RAHMAN (Rahman, et al., “Cell culture monitoring by impedance mapping…”, 2008 Physiol. Meas. 29 S227) and PELSTER (EP 0569572 B1), Applicant arguments (Pg.17, part e) focus on:
alleged differences between the disclosure of RAHMAN with limitations of claimed invention, with an argument that RAHMAN teaches away from limitations of claimed invention (Pg. 18-19);
argument of non-obviousness to combine PELSTER with RAHMAN (Pg. 19) based on an assertion that one of ordinary skill in the art “would not have turned to PELSTER, because PELSTER is non- analogous art”.
Examiner respectfully disagrees, with detailed reasoning below.
In considering recited limitations of Claims 1 and 18, Examiner asserts that RAHMAN is in same technical field, as noted in previous office action, teaching use of impedance spectroscopy of investigation of suspension. Applicant argues that RAHMAN “teaches a different setup-up and pursues an entirely different purpose”, based on RAHMAN teaching multiple measurements with multiple electrodes. Using plain meaning and broadest reasonable interpretation, with guidance from specification, Examiner respectfully disagrees and finds that RAHMAN does teach limitations as noted in previous office actions, where limitations as noted in arguments as distinguishing are recited by the combination with PELSTER. Applicant further argues that the claimed invention demonstrates “impedemetric sensor system than can map the cell distribution in the culture space”. However, examiner points to claim limitations as presented and does not find this inventive concept. While specification may be used to guide interpretation of claim limitations, examination must be focused on claim limitation language using interpretation as noted above.
Applicant further argues that RAHMAN may teach away from claimed invention. (Pg 19) Examiner respectfully disagrees. Specifically, Applicant argues (Pg. 18) RAHMAN teaches a “different set-up, and pursues an entirely different purpose”. Examiner respectfully disagrees. As noted in previous office action, RAHMAN is directed to the same technical field, specifically to measurement of impedance in a suspension using a multi-electrode configuration and a range of excitation frequencies. As noted in previous office action, PELSTER does teach a method for using a difference between two measured impedance values, where it would be reasonable to combine the inventive idea of PELSTER with the method and system of RAHMAN to arrive at the claimed invention.
Applicant further argues that one of ordinary skill would not have consulted PELSTER because PELSTER is not analogous art (Pg. ). Examiner respectfully disagrees using guidance found in MPEP 2141.01(a) I: “A reference is analogous art to the claimed invention if: (1) the reference is from the same field of endeavor as the claimed invention (even if it addresses a different problem); or (2) the reference is reasonably pertinent to the problem faced by the inventor (even if it is not in the same field of endeavor as the claimed invention).” Examiner has considered the problem faced by the inventor, based on claim limitations and guided by reading of specification
and understands the problem as directed to accurate and reliable determination of an impedance value of a suspension using impedance spectroscopy, namely in measuring impedance over a range of frequencies. Examiner finds that a person of ordinary skill would have reason to consult and apply the teachings found in the disclosure of RAHMAN, as noted above, as RAHMAN is explicitly directed to the same technical area. Further, PELSTER (referring to translated copy provided with previous office action)is directed to accurate and reliable determination of complex impedance, reciting a generalized method using a wide range of frequencies including detailed techniques for calibration ([0005]) and error correction ([0003], [0005], [0015]). While PELSTER does not disclose techniques aimed at a specific material or environment, PELSTER discloses important and relevant processes for performing electrode-based measurements of impedance which may be generally applied. Examiner asserts PELSTER would be considered by one of ordinary skill as “reasonably pertinent” to problem faced by Applicant.
Examiner finds claims as presently amended do not distinguish over cited prior art, with details discussed below.
Claim Rejections - 35 USC § 103
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, 2, 4, 6, 14-15, 18, and 44 are rejected under 35 U.S.C. 103 as being unpatentable over RAHMAN (Rahman, et al., “Cell culture monitoring by impedance mapping…”, 2008 Physiol. Meas. 29 S227), in view of PELSTER (EP 0569572 B1).
With respect to Claims 1 and 18, RAHMAN teaches:
A method for determining a value indicative of the impedance of a
suspension in the framework of an impedance spectroscopy, (RAHMAN is in same technical area, teaches use of impedance spectroscopy, Title: “Cell culture monitoring by impedance mapping using a multielectrode scanning impedance spectroscopy system”, and investigation of suspension, pS229, §2.1 “cell suspension on the microfabricated device”)
comprising the following steps:
generating an excitation current through the suspension, the excitation current oscillating at an excitation frequency; (RAHMAN teaches use of AC current for impedance measurements, detailed in Pg. S231, §2.3.: “impedance was recorded in the frequency range between 25 Hz and 1 MHz. A 10 mV amplitude signal was used as the excitation potential.”; RAHMAN teaches measurements in suspension, as above, pS229, §2.1 “cell suspension”; Examiner asserts one of ordinary skill in the art would understand frequency of current between electrodes would be implied based on frequency of time-dependent voltage applied between counter and working electrode in an impedance spectroscopy device.)
determining a first impedance measurement value on the basis of the excitation current and a first voltage at a first pair of measurement electrodes, (RAHMAN teaches sequential impedance measurements based on applied current using paired electrodes, Pg.S229, §2.1.: “eight-electrode array was used in monitoring cell behavior… Each one of the eight electrodes serves as an independent working electrode during multielectrode scanning.”; RAHMAN teaches sequential measurements with independent paired electrodes in Pg. S230, §2.2.: “In bipolar impedance measurements, the impedance is measured between two electrodes, a working and a counter electrode…working electrode was switched sequentially to record impedances of all eight electrodes against the common counter electrode”; Examiner interprets “first pair” as analogous to reference of the pairing of “working electrode” and “counter electrode”, as would be understood by one of ordinary skill in the art.)
determining a second impedance measurement value on the basis of the
excitation current and a second voltage at a second pair of measurement electrodes; (RAHMAN teaches paired electrodes for impedance measurement, as above, §2.1., RAHMAN teaches using eight independent electrodes for sequential impedance measurements, §2.2.: “the working electrode was switched sequentially to record impedances of all eight electrodes against the common counter electrode.”)
RAHMAN does not teach:
determining the value indicative of the impedance of the suspension by
correlating the first impedance measurement value and the second impedance measurement value,
wherein determining the value indicative of the impedance of the suspension comprises determining the difference between the first impedance measurement value and the second impedance measurement value, or comprises determining the difference between a first adjusted impedance value and a second adjusted impedance value, and wherein the first adjusted impedance value and the second adjusted impedance value are obtained by applying a correction function to the first impedance measurement value and the second impedance measurement value, the correction function representing the transmission behavior of the measurement arrangement.
PELSTER teaches:
determining the value indicative of the impedance of the suspension by correlating the first impedance measurement value and the second impedance measurement value. (Refer to translated copy, provided in previous office action; Examiner notes translation is annotated to include equations from original patent document; PELSTER is in a related technical area, and is determined to be pertinent art, as discussed above, Description, p1, [0001] and preamble to Claims 1 9: “method for determining electromagnetic impedances” and “determining the impedance of a capacitor arrangement, which consists of the two metal electrodes of the measurement cell and of the material between the areal regions”; PELSTER discloses method for using two impedance measurement to determine a impedance for matter between electrodes with a geometry and transmission factor in [0020]-[0024]; Examiner interprets “correlating” to mean generally an indication of how one variable is associated with another, analogous to reference, including, how impedance values are related according to geometric relationship, [0020] , via S parameters.)
wherein determining the value indicative of the impedance of the suspension comprises determining the difference between the first impedance measurement value and the second impedance measurement value, or comprises determining the difference between a first adjusted impedance value and a second adjusted impedance value, and wherein the first adjusted impedance value and the second adjusted impedance value are obtained by applying a correction function to the first impedance measurement value and the second impedance measurement value, the correction function representing the transmission behavior of the measurement arrangement. (PELSTER discloses, as above, a method for using differences between two impedance values measured with two distinct pairs of electrodes for determining a material impedance, Equation (4) and [0020]-[0024].)
It would have been obvious to one of ordinary skill in the art before effective filing date of the claimed invention to modify RAHMAN to determining the value indicative of the impedance of the suspension by correlating the first impedance measurement value and the second impedance measurement value and wherein determining the value indicative of the impedance of the suspension comprises determining the difference between the first impedance measurement value and the second impedance measurement value, such as that of PELSTER because it would provide a means of isolating the suspension properties while minimizing the impact of stray capacitance resulting from electrode configuration. This technique would be recognized by one of ordinary skill in the art as a way to reduce uncertainty in a value obtained for any matter between measurement electrodes. One of ordinary skill would be motivated to combine the multiple electrode method for impedance measurements as disclosed by RAHMAN, with the explicit relationships and processes for implementing electrode pair impedance determinations to find an accurate and reliable value for impedance in matter between electrodes, as taught by PELSTER, since it would not require significant alterations to the system disclosed by RAHMAN and would improve accuracy and reliability and provide a convenient way to extract intrinsic impedance of the material from the impedance properties of the actual measurement setup.
With respect to Claim 2, RAHMAN, in view of PELSTER, teaches the limitations of Claim 1.
RAHMAN further teaches:
wherein said first pair of measurement electrodes comprises a first measurement electrode and a second measurement electrode, and wherein said second pair of measurement electrodes comprises said first measurement electrode and a third measurement electrode
or
wherein the first pair of measurement electrodes comprises a first measurement electrode and a second measurement electrode, and wherein the second pair of measurement electrodes comprises a third measurement electrode and a fourth measurement electrode. (RHAMAN teaches at least a first pair of electrodes, and a second pair of electrodes, with eight independent working electrodes working in measurement process paired with a common ground electrode §2.1., §2.2.)
With respect to Claim 6, RAHMAN, in view of PELSTER, teaches limitations of Claim 1.
RHAMAN does not teach:
wherein determining the value indicative of the impedance of the suspension is carried out according to the following formula:
Z
=
k
1
λ
1
-
λ
2
G
e
l
-
1
Z
s
i
g
1
-
G
e
l
-
1
Z
s
i
g
2
wherein
Z
s
i
g
1
denotes the first impedance measurement value,
Z
s
i
g
2
denotes the second impedance measurement value,
G
e
l
-
1
denotes a correction function representing the transmission behavior of the measurement arrangement,
λ
1
denotes a first geometry factor representing the measurement geometry of the first pair of measurement electrodes,
λ
2
denotes a second geometry factor representing the measurement geometry of the second pair of measurement electrodes, and k denotes a proportionality constant.
PELSTER further teaches:
wherein determining the value indicative of the impedance of the suspension is carried out according to the following formula:
Z
=
k
1
λ
1
-
λ
2
G
e
l
-
1
Z
s
i
g
1
-
G
e
l
-
1
Z
s
i
g
2
wherein
Z
s
i
g
1
denotes the first impedance measurement value,
Z
s
i
g
2
denotes the second impedance measurement value,
G
e
l
-
1
denotes a correction function representing the transmission behavior of the measurement arrangement,
λ
1
denotes a first geometry factor representing the measurement geometry of the first pair of measurement electrodes,
λ
2
denotes a second geometry factor representing the measurement geometry of the second pair of measurement electrodes, and k denotes a proportionality constant. (PELSTER discloses method for using two impedance measurement to determine a impedance for matter between electrodes with a geometry and transmission factor, [0020]-[0024]; Examiner points specifically to discussion in [0022]: “measurements with two different impedances, Za and Zb, which are located between the electrodes instead of the impedance Z, are sufficient” and equation 4,:
PNG
media_image1.png
93
616
media_image1.png
Greyscale
; Examiner notes reference notation differs from application, but algebraic manipulation reveals an analogous expression as claim limitation, where impedance of suspension, noted as “Z” is taught as a function of measured impedance between electrode pairs (Za, Zb), with modification by transmission and geometric factors (shown as “S” factors) in equation, and found in [0024]: “ ;Examiners interpretation of an analogous representation is supported instant application specification, with definitions of the terms
G
e
l
-
1
and
λ
2
(p13, lines 10-15))
It would have been obvious to one of ordinary skill in the art before effective filing date of the claimed invention to further modify RAHMAN as modified by PELSTER as taught above, to include determination of a value indicative of the impedance of the suspension based on the equation shown above and a correction function and geometry factors for each electrode, and including a proportionality constant, such as that further disclosed by PELSTER because it would be seen as an advantage to use a known equation and process derived from fundamental consideration of the electrical properties of a electrochemical impedance spectroscopy system and basic principles and definitions of impedance. One of ordinary skill would recognize the value of using multiple electrodes to directly measure impedance values that make it possible to determine an accurate and reliable value of an unknown suspension impedance, by eliminating stray electric field effects due to capacitive properties of electrode, as disclosed in PELSTER.
With respect to Claim 14, RAHMAN, in view of PELSTER, teaches the limitations of claim 1.
RAHMAN further teaches:
further comprising: determining a third impedance measurement value on the basis of the excitation current and a third voltage at a third pair of measurement electrodes; (RAHMAN teaches, as above, impedance measurements using an 8 electrode system, to make independent measurements for comparison, FIGs 1 and 2, with 2.2. “impedance is measured between two electrodes, a working and a counter electrode. In the multiple working electrode system (multielectrode array) used in this work, the working electrode was switched sequentially to record impedances of all eight electrodes against the common counter electrode”.
RAHMAN does not teach:
and determining the value indicative of the impedance of the suspension by correlating the first impedance measurement value, the second impedance measurement value, and the third impedance measurement value.
PELSTER further teaches:
and determining the value indicative of the impedance of the suspension by correlating the first impedance measurement value, the second impedance measurement value, and the third impedance measurement value. (PELSTER teaches, as above method of using measured impedance values combined for determination of unknown impedance of suspension material, [0020]-[0024]; Examiner asserts one of ordinary skill would realize the novel process taught by PELSTER for electrode pairs is extendable to multiple electrode pairs, such as those of RAHMAN)
It would have been obvious to one of ordinary skill in the art before effective filing date of the claimed invention to further modify RAHMAN, as modified by PELSTER as taught above, to include a third electrode pair for determining as disclosed by the combination of RAHMAN with PELSTER because it would be recognized as a way to increase the accuracy and reliability of suspension impedance determination by further eliminated artifacts due to geometry of the system. One of ordinary skill would see the advantage of using multiple measurements for improving overall value of the impedance measurement without compromising efficiency.
With respect to Claim 15, RAHMAN, in view of PELSTER, teaches the limitations of claim 14.
RAHMAN further teaches:
wherein determining the value indicative of the impedance of the suspension comprises determining a first difference between the first impedance measurement value and the second impedance measurement value and determining a second difference between the first impedance measurement value and the third impedance measurement value and determining a third difference between the second impedance measurement value and the third impedance measurement value, (RAHMAN teaches at least the first of the “or” list; RAHMAN teaches, as above, impedance measurements using an 8 electrode system, FIGs 1,2, with § 2.2. “impedance is measured between two electrodes, a working and a counter electrode. In the multiple working electrode system (multielectrode array) used in this work, the working electrode was switched sequentially to record impedances of all eight electrodes against the common counter electrode”)
With respect to Claim 44, RAHMAN, in view of PELSTER teaches limitations of Claim 1.
RAHMAN further teaches:
A computer program comprising program instructions which, when executed on a data processing system, perform a method according to claim 1. (RAHMAN teaches standard use of computer interfacing for impedance measuring device in §2.3.: “instrumentation was set up to acquire data automatically over a period of time using the programming capability”)
Claims 5 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over RAHMAN, in view of PELSTER, as applied to Claim 1 above, and further in view of GAWAD (GAWAD, et al., “Micromachined impedance spectroscopy flow cytometer for cell analysis and particle sizing”, Lab on a Chip, 2001, 1, 76–82)
With respect to Claim 5, RAHMAN, in view of PELSTER, teaches the limitations of claim 1.
RAHMAN, as modified by PELSTER as taught above, does not teach:
wherein determining the value indicative of the impedance of the suspension comprises determining the difference between a first geometry factor and a second geometry factor, and
wherein the first geometry factor represents the measurement geometry of the first pair of measurement electrodes and wherein the second geometry factor represents the measurement geometry of the second pair of measurement electrodes.
GAWAD teaches:
wherein determining the value indicative of the impedance of the suspension comprises determining the difference between a first geometry factor and a second geometry factor, (GAWAD is in same technical field, Abstract, p1: “device measures the spectral impedance of individual cells or particles”; GAWAD teaches use of multiple electrodes, P78, Col2: “A total of 8 electrodes are available on the current chip design (Fig. 6)”, and consideration of geometry factors, Abstract,p.1: “simulations are presented to compare various electrode geometries and their influence on cell parameters estimation… impedance signal is recorded by a differential pair of microelectrodes using the cell surrounding media as a reference”, and P7, Col2: “Three electrode geometries are compared to the analytical solution”, with Figure 1, depicting how two pairs of electrodes are compared.)
wherein the first geometry factor represents the measurement geometry of the first pair of measurement electrodes and wherein the second geometry factor represents the measurement geometry of the second pair of measurement electrodes. (GAWAD teaches the geometry effect of each electrode configuration, as above, Abstract, p1 )
It would have been obvious to one of ordinary skill in the art before effective filing date of the claimed invention to further modify RAHMAN, as modified by PELSTER as taught above, to include the step of determining the value indicative of the impedance of the suspension comprises determining the difference between a first geometry factor and a second geometry factor, and wherein the first geometry factor represents the measurement geometry of the first pair of measurement electrodes and wherein the second geometry factor represents the measurement geometry of the second pair of measurement electrodes, such as that of GAWAD because it would be understood that impedance measurements would include properties of the measurement electrodes and their arrangement in the measurement cell or device. One of ordinary skill would understand and realize the advantage of consideration of geometric factors as disclosed by GAWAD in a system such as that of RAHMAN as modified by PELSTER, in determination of a reliable and accurate impedance of the suspension under test.
With respect to Claim 7, RAHMAN, in view of PELSTER, teaches the limitations of claim 1.
RAHMAN does not teach:
further comprising: measuring the first voltage at the first pair of measurement electrodes;
and measuring the second voltage at the second pair of measurement electrodes, wherein measuring the first voltage and measuring the second voltage are performed substantially simultaneously or in a time-shifted manner.
PELSTER further teaches:
further comprising: measuring the first voltage at the first pair of measurement electrodes, and measuring the second voltage at the second pair of measurement electrodes, (PELSTER teaches impedance measurements involve voltage measurements, [0003]: “a that current and voltage along the transmission line change as a function of location, deviating from the electrical description”, and [0018]: “related to the voltage measured in the detector DT of the reference arm, whereby the terminating impedances are realized by the detectors themselves”)
It would have been obvious to one of ordinary skill in the art before effective filing date of the claimed invention to modify RAHMAN, as modified by PELSTER as taught above, to include measuring the first voltage at the first pair of measurement electrodes, and measuring the second voltage at the second pair of measurement electrodes, such as that further disclosed by PELSTER because it would be understood that voltage measurements are required to determine artifacts present in impedance measurements due to transmission properties that should be taken into account to determine suspension impedance accurately, as discussed in PELSTER’s disclosure.
RAHMAN, as modified by PELSTER as taught above does not teach:
wherein measuring the first voltage and measuring the second voltage are performed substantially simultaneously or in a time shifted manner
GAWAD further teaches:
wherein measuring the first voltage and measuring the second voltage are performed substantially simultaneously or in a time shifted manner (GAWAD teaches simultaneous impedance measurement, Abstract: “micromachined chip and processing electronic circuit allow simultaneous impedance measurements at multiple frequencies”)
It would have been obvious to one of ordinary skill in the art before effective filing date of the claimed invention to further modify RAHMAN, as modified by PELSTER as taught above, to include measuring the first voltage and measuring the second voltage are performed substantially simultaneously, such as that of GAWAD because it would be known as way to provide a comprehensive and detailed understanding of a complex electrochemical system, particularly in determining differences between processes occurring a spatially distinct locations or at interfaces within the same system. One of ordinary skill would see the advantage of combining the simultaneous measurement technique taught by GAWAD with the system and method of RAHMAN as modified by PELSTER to improve the ability to separate system properties from the unknown impedance of the suspension.
Claims 10 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over RAHMAN, in view of PELSTER, as applied to claim 1, and further in view of HARPE (US 20170071552 A1).
With respect to Claim 10, RAHMAN, in view of PELSTER, teaches the limitations of claim 1.
RAHMAN does not teach:
wherein determining the first impedance measurement value and determining the second impedance measurement value comprises: sampling the excitation current, sampling the first voltage, and sampling the second voltage;
wherein the method further comprises the steps of: setting a first sampling rate for sampling the excitation current, setting a second sampling rate for sampling the first voltage, and setting a third sampling rate for sampling the second voltage,
wherein the first sampling rate, the second sampling rate and the third sampling rate are set to at least 4 times the excitation frequency of the excitation current.
PELSTER further teaches:
wherein determining the first impedance measurement value and determining the second impedance measurement value comprises: sampling the excitation current, sampling the first voltage, and sampling the second voltage; (PELZER teaches, as above, acquisition of voltage and current for each electrode configuration, [0003]: “these and the effects of multiple reflections must be taken into account when determining impedance in order to determine the actual voltage-current relationship by which the impedance is defined”; [0018]: “voltage source Q supplies a sinusoidal signal…fed via a power divider LT into the sample arm, which contains the measuring cell, and into the reference arm…voltage ratio at the terminating impedances in the sample and reference arms is measured according to magnitude and phase”)
It would have been obvious to one of ordinary skill in the art before effective filing date of the claimed invention to further modify RAHMAN, as modified by PELSTER as taught above, to include sampling the excitation current, sampling the first voltage, and sampling the second voltage for determining the first impedance measurement value and determining the second impedance measurement value, such as that of PELSTER because this technique would improve the accuracy impedance determination by isolating the impedance under test from errors that may be introduces by hardware and/or other environmental factors, including polarization effects.
RAHMAN, as modified by PELSTER as taught above, does not teach:
wherein the method further comprises the steps of: setting a first sampling rate for sampling the excitation current, setting a second sampling rate for sampling the first voltage, and setting a third sampling rate for sampling the second voltage,
wherein the first sampling rate, the second sampling rate and the third sampling rate are set to at least 4 times the excitation frequency of the excitation current, in particular to substantially 4 times the excitation frequency of the excitation current.
HARPE teaches:
wherein the method further comprises the steps of: setting a first sampling rate for sampling the excitation current, setting a second sampling rate for sampling the first voltage, and setting a third sampling rate for sampling the second voltage, (HARPE is in same technical field, Abstract: “directed to an impedance spectroscopy system for bio-impedance measurement” and [0004]: “injecting a low-level AC current to a body segment, a voltage proportional to the tissue impedance can be measured”; HARPE teaches analogous measurement sampling rates, [0056]: “MLS [maximal length sequence] sequence has frequency components at fsk/(2n−1), where fs is the MLS sampling frequency, n is the MLS order and 0<k<2n−1”; )
wherein the first sampling rate, the second sampling rate and the third sampling rate are set to at least 4 times the excitation frequency of the excitation current, in particular to substantially 4 times the excitation frequency of the excitation current. (HARPE teaches increase in sampling rates in [0057]: “bio-impedance is typically measured at high frequencies (10 kHz-100 kHz) where current starts penetrating into the cell as shown in FIG. 1.”; HARPE teaches excitation frequency at least 4 time the excitation frequency, [0066]: “bio-impedance is usually measured above 1 kHz, the injected MLS signal can be adjusted to only contain energy above 1 kHz (or only above a lower threshold such as 300 Hz or 100 Hz)”)
It would have been obvious to one of ordinary skill in the art before effective filing date of the claimed invention to further modify RAHMAN, as modified by PELSTER as taught above, to include the steps of: setting a first sampling rate for sampling the excitation current, setting a second sampling rate for sampling the first voltage, and setting a third sampling rate for sampling the second voltage, to improve a method for determination of impedance, such as that of HARPE because it would allow for optimization of a sampling frequency specific to a particular sample, which would be seen as particularly important when measuring biological samples. One of ordinary skill would also understand this combination of sample rate selection as taught by HARPE with the method and system of RAHMAN as modified by PESTER, would also allow for optimizing measurements based on geometry and configurations of electrodes and suspension volume. One of ordinary skill would be further motivated based on HARPE’s disclosure that increasing frequency of an injection current would mean increased power, and would not be as efficient in evaluating material response, since typical bio-impedance behavior has a low pass frequency characteristic, i.e., impedance is greater at lower frequencies and therefore more easily measured with measurement sampling rates much higher. One of ordinary skill would understand combining the technique of HARPE with the system and method of RAHMAN as modified by PELSTER would result in an improved signal to noise ratio which would be flattened with respect to frequency and provide a more reliable signal to noise ratio during a full spectral analysis.
With respect to Claim 13, RAHMAN, in view of PELSTER and further in view of HARPE teaches the limitations of claim 10.
RAHMAN, as modified by PELSTER as taught above, does not teach:
wherein the step of determining the first impedance measurement value comprises performing a first complex Fourier transform on the basis of the sampling values of the excitation current and the sampling values of the first voltage, and wherein the step of determining the second impedance measurement value comprises performing a second complex Fourier transform on the basis of the sampling values of the excitation current and the sampling values of the second voltage.
HARPE further teaches:
wherein the step of determining the first impedance measurement value comprises performing a first complex Fourier transform on the basis of the sampling values of the excitation current and the sampling values of the first voltage, and wherein the step of determining the second impedance measurement value comprises performing a second complex Fourier transform on the basis of the sampling values of the excitation current and the sampling values of the second voltage. (HARPE teaches using FFT to determine impedance in [0050]: “digital signal processing comprises spectral analysis using a Fast Fourier Transform (FFT)…From the spectral analysis, a complex impedance is derived as a function of frequency, in unit 42…magnitude and phase of the bio-impedance is thereby determined”)
It would have been obvious to one of ordinary skill in the art before effective filing date of the claimed invention to further modify RAHMAN, as modified by PELSTER and HARP as taught above, to include performing a first complex Fourier transform on the basis of the sampling values of the excitation current and the sampling values [as described above] for determining impedance for each measured voltage to determine impedance, such as that further disclosed by HARPE because implementing this mathematical technique would be a more efficient way to conduct a wide-ranging spectroscopic investigation of sample properties. One of ordinary skill would see the FFT method as taught by HARPE as an obvious logical combination with the system and method of RAHMAN as modified by PELSTER, since application of the FFT algorithm to the response signal would allow for simultaneous wide-range frequency acquisition and reduce overall measurement time for the process, resulting in a reasonable expectation of improving efficiency of determination of suspension impedance.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over RAHMAN, in view of PELSTER, as applied to Claim 1, and further in view of DOWNEY (US 20150019140 A1).
With respect to Claim 19, RAHMAN, in view of PELSTER teaches the limitations of Claim 1.
RAHMAN further teaches:
A method for deriving at least one characteristic property of a suspension,
comprising the steps of: performing the method for determining a value indicative of the impedance of a suspension according to claim 1, (as above, Claim 1)
RAHMAN does not teach:
performing method a plurality of times, using a plurality of different excitation frequencies and determining a plurality of values indicative of the impedance of the suspension for the plurality of different excitation frequencies;
deriving a plurality of values indicative of the permittivity of the suspension based on the plurality of values indicative of the impedance of the suspension; and
deriving the at least one characteristic property of the suspension by correlating the plurality of values indicative of the permittivity of the suspension.
PELSTER further teaches:
performing method a plurality of times, using a plurality of different excitation frequencies and determining a plurality of values indicative of the impedance of the suspension for the plurality of different excitation frequencies; (PELSTER teaches, as multiple, sequential measurements and frequency range for excitation and measurement, [0004]: “Influences of the supply lines are eliminated in a 3-step procedure…”one after the other and the reflection and transmission coefficients are measured…various measurement methods in the frequency range between 0 and 10 GHz are described as state of the art.”)
It would have been obvious to one of ordinary skill in the art before effective filing date of the claimed invention to further modify RAHMAN, as modified by PELSTER as taught above, to including performing method a plurality of times using a plurality of different excitation frequencies and determining a plurality of values indicative of the impedance of the suspension for the plurality of different excitation frequencies, such as that further disclosed by PELSTER because this repetitive method based on multiple measurements would result in a more reliable and accurate determination of a suspension impedance value and provide a way to validate measured values.
RAHMAN, as modified by PELSTER as taught above, does not teach:
deriving a plurality of values indicative of the permittivity of the suspension based on the plurality of values indicative of the impedance of the suspension; and
deriving the at least one characteristic property of the suspension by correlating the plurality of values indicative of the permittivity of the suspension.
DOWNEY teaches:
deriving a plurality of values indicative of the permittivity of the suspension based on the plurality of values indicative of the impedance of the suspension, and (DOWNEY is in same technical field, Abstract: “Methods and apparatus are disclosed for correcting measurements received by applying a frequency-varying signal with a measuring device (e.g., a permittivity probe)”, DOWNEY teaches impedance related to permittivity, [0003]: “including techniques that count cells based on electrical impedance”; with technique applied to measuring properties of a suspension, [0011]: “measuring devices used in performing dielectric spectroscopy operate by detecting a capacitance, or ability to store electrical charge, of cells in a population (e.g., a suspension of cells)”)
deriving the at least one characteristic property of the suspension by correlating the plurality of values indicative of the permittivity of the suspension. (DOWNEY teaches deriving at least one property based on permittivity measurements, FIG. 3 with [0030]: “FIG. 3 is a graph illustrating viability versus permittivity ratio for determining a relationship between biological property data and electrical property data obtained at two-frequencies”)
It would have been obvious to one of ordinary skill in the art before effective filing date of the claimed invention to further modify RAHMAN, as modified by PELSTER as taught above, to include deriving a plurality of values indicative of the permittivity of the suspension based on the plurality of values indicative of the impedance of the suspension, and deriving the at least one characteristic property of the suspension by correlating the plurality of values indicative of the permittivity of the suspension, such as that of DOWNEY because using evaluation of both of such measurements would allow for a more comprehensive evaluation of a the fundamental electrical response of a material. One of ordinary skill would see the advantage of deriving the at least one characteristic property of the suspension by correlating the plurality of values indicative of the permittivity of the suspension because it would be an efficient way to use data being measured for impedance, and easily possible due to the relationship between impedance and permittivity in a material. It would be seen as an advantage to monitor permittivity since it could lead to an enhanced understanding of a material, including cell viability, membrane integrity, particle concentration an size, and even binding and interactions between particles.
Claim 22 is rejected under 35 U.S.C. 103 as being unpatentable over RAHMAN in view of PELSTER and DOWNEY, as applied to claim 19, and further in view of GAWAD.
With respect to Claim 22, RAHMAN, in view of PELSTER, and further in view of DOWNEY, teaches the limitations of Claim 19.
RAHMAN, as modified by PELSTER and DOWNEY as taught above, does not teach:
wherein deriving the at least one characteristic property of the suspension includes generating a curve of the values indicative of the permittivity of the suspension over the different excitation frequencies.
and/or
wherein the suspension is a cell population and wherein the at least one characteristic property of the suspension comprises at least one property of number of living cells, size of the cells and homogeneity of the cells.
GAWAD teaches
wherein the suspension is a cell population and wherein the at least one characteristic property of the suspension comprises at least one property of number of living cells, size of the cells and homogeneity of the cells. (GAWAD teaches measuring properties of a suspension, Abstract: “ impedance measurements of cells and particles of different sizes and types to demonstrate the differentiation of subpopulations in a mixed sample” and page 80, col 1: “latex beads were used to determine whether our system was able to differentiate particles of different sizes.”; Examiner notes interpretation of claim limitation language “homogeneity” to be analogous to reference process of determining and differentiating varying particle sizes in a suspension.)
It would have been obvious to one of ordinary skill in the art before effective filing date of the claimed invention to modify RAHMAN, as modified by PELSTER and DOWNEY as taught above, to include investigation of suspension that is a cell population and wherein the at least one characteristic property of the suspension comprises at least one property of number of living cells, size of the cells and homogeneity of the cells, such as that of GAWAD because such evaluation would provide important characterization and monitoring of cell properties within a suspension in a label-free, real-time, and non-destructive manner. One of ordinary skill would see the advantage of including the technique taught by GAWAD in combination with the method/system disclosed by RAHMAN, as modified by PELSTER and DOWNEY, as an advantage because the technique utilizes measurements already planned for the system to reveal new properties of cells within the suspension.
Claims 24-25, 27, 31, 43 are rejected under 35 U.S.C. 103 as being unpatentable over TODD (EP 2405263 B1) in view of PELSTER.
Examiner notes typographical error in previous office action where Claim 40 was enumerated in this rejection statement.
With respect to Claims 24 and 43, TODD teaches:
A sensor for determining a value indicative of the impedance of a suspension, comprising an oscillator circuit; (TODD is in same technical area, [0001]: “invention relates a method and apparatus for analysis of a dielectric medium”; TODD discloses oscillator circuit used for measurement, FIG. 2 - Examiner notes correction of type-o from previous office action for figure number; TODD explicitly teaches time-varying excitation in circuit [0003]: “techniques involve introducing metal electrodes into the liquid and applying an excitation signal (usually sinusoidal) and measuring voltage and current using a pair of measurement electrodes”; and ;measurement of impedance in suspension, [0034]: “at the high excitation frequencies, the impedance of the suspension/electrode interface is negligibly small compared to that of the liquid or suspension.”)
a pair of excitation electrodes coupled to the oscillator circuit, wherein an excitation current through the suspension, oscillating at an excitation frequency, can be generated across the pair of excitation electrodes by means of the oscillator circuit; (TODD teaches paired electrodes in oscillator circuit, as above, FIG. 2 with [0003]; TODD discloses pairs of electrodes for excitation signal [0014]: “the second couple of electrodes may comprise one of the excitation electrodes and a sensing electrode.”)
at least three measurement electrodes for measuring a first voltage in the suspension between a first pair of the at least three measurement electrodes and a second voltage in the suspension between a second pair of the at least three measurement electrodes, and (TODD teaches circuit with four electrodes, FIG. 2, with description of electrodes, as above, [0003]; TODD apparatus for measuring suspension, as above, and [0010]: “apparatus comprises electrodes placed in a suspension where an alternating current voltage is applied between the electrodes”; TODD discloses at least two pairs of electrodes for excitation signal and measurement [0016]: “first couple of electrodes comprise first and second sensing electrodes (for example a pair of electrodes); and a second couple of electrodes comprise first and second excitation electrodes for applying the excitation current to the test medium, and the measured voltages across the excitation electrodes and the sensing electrodes are compared”)
a data processing device (TODD discloses calculation of impedance, [0003]: “techniques involve introducing metal electrodes into the liquid and applying an excitation signal (usually sinusoidal) and measuring voltage and current using a pair of measurement electrodes. The impedance, conductivity and specific capacitance can then be calculated.”; using standard computational processing, [0037]: “by means of known algorithms running on conventional processors or computer software”)
TODD does not teach:
a data processing device configured to determine a first impedance measurement value on the basis of the excitation current and the first voltage, to determine a second impedance measurement value on the basis of the excitation current and the second voltage, and to determine the value indicative of the impedance of the suspension by correlating the first impedance measurement value and the second impedance measurement value,
wherein the data processing device is configured to determine the value indicative of the impedance of the suspension via determining the difference between the first impedance measurement value and the second impedance measurement value, or wherein the data processing device is configured to determine the value indicative of the impedance of the suspension via determining the difference between a first adjusted impedance value and a second adjusted impedance value, wherein the data processing device is configured to determine the first adjusted impedance value and the second adjusted impedance value by applying a correction function to the first impedance measurement value and the second impedance measurement value, wherein the correction function represents the transmission behavior of the measurement arrangement.
PELSTER teaches:
a data processing device configured to determine a first impedance measurement value on the basis of the excitation current and the first voltage, to determine a second impedance measurement value on the basis of the excitation current and the second voltage, and to determine the value indicative of the impedance of the suspension by correlating the first impedance measurement value and the second impedance measurement value. (PELSTER teaches, as above, method for using two impedance measurement to determine a impedance for matter between electrodes with a geometry and transmission factor in [0020]-[0024].)
wherein the data processing device is configured to determine the value indicative of the impedance of the suspension via determining the difference between the first impedance measurement value and the second impedance measurement value (PELSTER teaches, as above, Claims 1 and 18, method for using differences between two impedance values measured with two distinct pairs of electrodes for determining a material impedance, Equation (4) and [0020]-[0024])
It would have been obvious to one of ordinary skill in the art before effective filing date of the claimed invention to modify TODD to include configuration of a sensor data processing device to determine a first impedance measurement value on the basis of the excitation voltage and the first current, to determine a second impedance measurement value on the basis of the excitation voltage and the second current, and to determine the value indicative of the impedance of the suspension by correlating the first impedance measurement value and the second impedance measurement value, and to determine the value indicative of the impedance of the suspension via determining the difference between the first impedance measurement value and the second impedance measurement value such as that of PELSTER because it would be understood as an effective way to take advantage of sequential measurements made by multiple electrodes to enhance the accuracy and reliability of impedance values derived from those measurements. One of ordinary skill would see the advantage of combining the technique of PELSTER with the disclosure of a sensor as taught by TODD because analysis of two different impedance values would reveal distinct electrochemical phenomena that may occur in a suspension.
With respect to Claim 25, TODD in view of PELSTER teaches limitations of claim 24.
TODD further teaches:
wherein the at least three measurement electrodes are arranged between the pair of excitation electrodes.(TODD teaches this arrangement of electrodes for impedance measurement, [0040]: “technique in accordance with the invention a three electrode system may be used”’ and [0041]: “As shown in figure 3, the two outer electrodes 43,44 form a first electrode couple and are used to drive current through the sample.”)
With respect to Claim 27, TODD in view of PELSTER teaches the limitations of claim 24.
TODD further teaches:
wherein the sensor comprises at least four measurement electrodes, wherein the first pair of the at least four measurement electrodes comprises a first measurement electrode and a second measurement electrode and wherein the second pair of the at least four measurement electrodes comprises a third measurement electrode and a fourth measurement electrode (TODD teaches circuit with at least four electrodes, as above, FIG. 2, with [0003], and teaches at least two pairs of electrodes for measurement, [0010])
wherein the third and fourth measurement electrodes are arranged between the first and second measurement electrodes and/or wherein the third and fourth measurement electrodes are arranged on a different side of the sensor than the first and second measurement electrodes. (TODD teaches paired electrodes arranged in this manner, as above, FIG. 2 with [0003])
With respect to Claim 31, TODD, in view of PELSTER, as taught above, teaches limitation of Claim 24.
TODD further teaches:
wherein the data processing device is configured to determine the value indicative of the impedance of the suspension (TODD discloses calculation of impedance, as above, [0003] and use of standard computational processing, [0037].)
TODD does not teach:
PELSTER further teaches:
determine the value indicative of the impedance of the suspension via determining the difference between a first geometry factor and a second geometry factor, wherein the first geometry factor represents the measurement geometry of the first pair of the at least three measurement electrodes and wherein the second geometry factor represents the measurement geometry of the second pair of the at least three measurement electrodes,
wherein the data processing device is configured to determine the value indicative of the impedance of the suspension according to the following formula:
Z
=
k
1
λ
1
-
λ
2
G
e
l
-
1
Z
s
i
g
1
-
G
e
l
-
1
Z
s
i
g
2
[AltContent: ]wherein
Z
s
i
g
1
denotes the first impedance measurement value,
Z
s
i
g
2
denotes the second impedance measurement value,
G
e
l
-
1
denotes a correction function representing the transmission behavior of the measurement arrangement,
λ
1
denotes a first geometry factor representing the measurement geometry of the first pair of the at least three measurement electrodes,
λ
2
denotes a second geometry factor representing the measurement geometry of the second pair of the at least three measurement electrodes, and
k
denotes a proportionality constant. (PELSTER teaches this method, as above, as explained in detail addressing parallel limitation in claim 6, for using two impedance measurement to determine a impedance for matter between electrodes with a geometry and transmission factor in [0020]-[0024], with discussion of mathematically analogous equation (4) in reference)
Allowable Subject Matter
Claims 16, 20, and 40 are objected to as being dependent upon a rejected base claim (with direct or indirect dependency to Claim 1 and Claim 24) but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. Examiner notes typographical error in omission of Claim 40, which was discussed as allowable subject matter in previous office action but omitted from list in first sentence.
The following is a statement of reasons for the indication of allowable subject matter:
Specifically regarding Claim 16, the closest prior art fails to disclose nor would it be obvious to combine identified prior art to arrive at the claim limitation of “determining the value indicative of the impedance of the suspension is carried out according to the following formula:
Z
2
=
k
2
λ
3
G
e
l
-
1
Z
s
i
g
2
-
G
e
l
-
1
Z
s
i
g
2
λ
1
-
λ
2
λ
1
-
λ
3
λ
2
-
λ
3
+
k
2
λ
2
G
e
l
-
1
Z
s
i
g
12
-
G
e
l
-
1
Z
s
i
g
3
λ
1
-
λ
2
λ
1
-
λ
3
λ
2
-
λ
3
+
k
2
λ
1
G
e
l
-
1
Z
s
i
g
3
-
G
e
l
-
1
Z
s
i
g
2
λ
1
-
λ
2
λ
1
-
λ
3
λ
2
-
λ
3
wherein
Z
s
i
g
1
denotes the first impedance measurement value,
Z
s
i
g
2
denotes the[AltContent: ] second impedance measurement value,
Z
s
i
g
3
denotes the third impedance measurement value,
G
e
l
-
1
denotes a correction function that represents the transmission behavior of the measurement arrangement,
λ
1
denotes a first geometry factor that represents the measurement geometry of the first pair of measurement electrodes,
λ
2
denotes a second geometry factor that represents the measurement geometry of the second pair of measurement electrodes,
λ
3
denotes a third geometry factor that represents the measurement geometry of the third pair of measurement electrodes, and
k
2
denotes a proportionality constant.” While PELSTER does teach a method for using paired electrodes for determination of a material impedance for a suspension or fluid based on impedance measures between paired electrodes, the equation that extends the method to three electrodes in this particular form was not discovered. Thus the limitation, in combination with all other required limitations of the claim on which Claim 16 has dependency renders the claim allowable over identified prior art.
Specifically regarding Claim 40, the closes prior art fails to disclose nor would it be obvious to combine with other identified and relevant prior art the claim limitation of “oscillator circuit is coupled to the pair of excitation electrodes via a transformer, wherein the transformer in particular has a parallel capacitance of 0.5 to 10 pF”. Examiner finds the specificity of the capacitance for the transformer is not disclosed in prior art. While one of ordinary skill would understand the necessity and role of a transformer in an oscillator circuit integrated within and EIS system, the particular capacitance as recited in the claim limitation would be specific to a particular system and particular application. Examiner found that the capacitance for transformers found in closest prior art (for example, PELSTER) was not quantitatively specified, and thus the specific range as claimed in the instant application would not be obvious. Thus, this limitation in combination with all other limitations of the claim and the claims on which it has dependency renders the claim allowable over prior art.
Any comments considered necessary by applicant must be submitted no later than the payment of the issue fee and, to avoid processing delays, should preferably accompany the issue fee. Such submissions should be clearly labeled “Comments on Statement of Reasons for Allowance.”
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure was included in previous office action.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TONI D SAUNCY whose telephone number is (703)756-4589. The examiner can normally be reached Monday - Friday 8:30 a.m. - 5:30 p.m. ET.
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/TONI D SAUNCY/Examiner, Art Unit 2857
/Catherine T. Rastovski/Supervisory Primary Examiner, Art Unit 2857