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 .
Response to Arguments
Amendments to claims dated 07/23/2026 have been fully reviewed and are accepted.
Claims 1-2, 7, 10, 13-16, 18-20, 22, 24-25, 27, 40 and 43-44 are pending in this office action.
Claims 5-6 and 31 are cancelled.
Claims 1, 14, 15, 16, 18, 19, 24, and 43 are amended.
In previous office action (Final Rejection dated 03/23/2026), Claims 1-2, 5-7, 10, 13-15, 18-19, 22, 24-25, 27, 31, and 43-44 were rejected under 35 U.S.C. § 103 and
Claims 16, 20, and 40 were objected to as being dependent on a rejected base claim but would be allowable if rewritten in independent form.
Regarding rejection under 35 U.S.C. § 103
Applicant’s arguments regarding rejections under 35 U.S.C. § 103 in previous office action (Final Rejection dated 07/23/2026) over prior art have been fully reviewed and fully considered but are not persuasive.
Specifically, Applicant argues lack of an obvious combination for one of ordinary skill in the art (Remarks, Pg16/25, last paragraph) in rejection of Claim 1, rejection in previous office action over prior art by RAHMAN (“Cell culture…) in an obvious combination with PELSTER (EP0569572 B1). Examiner respectfully disagrees. Applicant’s arguments are directed to Claim 1, as presently amended, which includes matter previously recited in Claim 6 (now cancelled). In response to Applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, Examiner notes that the matter recited in Claim 6 was also rejected over prior art by RAHMAN in combination with PELSTER. Examiner notes that neither RAHMAN nor PELSTER individually teach all limitations of Claim 1 or Claim 6, but it is consideration of the combination of the teachings that one of ordinary skill in the art could arrive with a reasonable expectation of success at the claimed invention. With guidance from MPEP 2120 III., Examiner notes “in a rejection based on 35 U.S.C. 103, the reference teachings must somehow be modified in order to meet the claims. The modification must be one which would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention” Further, Examiner points to guidance found in MPEP 2141 for general discussion of obviousness and MPEP 2143, I. with guidance of rationales that support a conclusion of obviousness, noting specifically, G. where in obviousness relies on findings in prior art and knowledge of one of ordinary skill in the art aimed at establishing appropriate rationale for motivation to combine using Graham v. Deere factual inquiry. Examiner notes that both RAHMAN, with disclosure directed to impedance spectroscopy, and PELSTER, with disclosure directed to accurate and reliable determination of complex impedance, serve as appropriate and reasonable references with overlapping, but not identical subject matter that one of ordinary skill would find reason to combine.
Further, Applicant argues that PELSTER is non analogous art (Remarks Pg20, last paragraph). Examiner respectfully disagrees and notes that this argument was addressed fully in previous office action. In response, Examiner points out as previously, it has been held that a prior art reference must either be in the field of the inventor’s endeavor or, if not, then be reasonably pertinent to the particular problem with which the inventor was concerned, in order to be relied upon as a basis for rejection of the claimed invention. See In re Oetiker, 977 F.2d 1443, 24 USPQ2d 1443 (Fed. Cir. 1992). In this case, using Applicant’s specification for guidance in understanding claimed invention, Examiner finds that one of ordinary skill in the art would find reason to consult the reference by PELSTER in seeking a solution to the stated problem. Examiner points, as in previous office action, to 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), as noted above, is also 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 to a wide range of materials and systems. Examiner asserts that one of ordinary skill would find value in the teaching of PELSTER and consider the subject matter to be “reasonably pertinent” to problem faced by Applicant.
Applicant further argues that the combination of RAHMAN and PELSTER is based on impermissible hindsight (PG21, second paragraph), arguing “Pelster discloses a formula relating impedance measurements does not, without more, motivate the skilled person toward the specific differential, dual-electrode-pair, same-suspension measurement approach”. Examiner respectfully disagrees. The references are both directed to measurement of impedance and a person of ordinary skill would have reason to consult both references. In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). Further, Examiner points again to guidance found in MPEP 2142 in discussion of avoiding hindsight in reaching conclusions based on obvious combination, reciting “35 U.S.C. 103 authorizes a rejection where, to meet the claim, it is necessary to modify a single reference or to combine it with one or more other references”. Using broadest reasonable interpretation of claim limitations consistent with the specification, and MPEP guidance regarding expectation for forming a prima facie case of obviousness to avoid hindsight, Examiner asserts that cited prior art would be reasonably consulted by one of ordinary skill in the art on or before the effective filing date of the claimed invention, and would find rationale for combining the teachings to arrive at the claimed invention.
As noted above, Examiner has fully considered Applicant’s arguments, but they are unpersuasive, with new grounds of rejection made based on amendments.
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, 14, 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
(Claim 1) 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:
(Claim 1) generating an excitation current through the suspension, the excitation current oscillating at an excitation frequency;
(Claim 18) generating an excitation voltage, oscillating at an excitation frequency, applied to the suspension (RAHMAN teaches use of AC current for impedance measurements, 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.”; teaches measurements in suspension, as above, pS229, §2.1 “cell suspension”; Examiner interprets “excitation voltage” to be analogous to reference “10 mV amplitude signal”. Examiner asserts that 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.)
(Claim 1) determining a first impedance measurement value of the suspension on the basis of the excitation current and a first voltage at a first pair of measurement electrodes,
(Claim 18) determining a first impedance measurement value of the suspension on the basis of the excitation voltage and a first current 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.)
(Claim 1) determining a second impedance measurement value of the suspension on the basis of the excitation current and a second voltage at a second pair of measurement electrodes;
(Claim 18) determining a second impedance measurement value of the suspension on the basis of the excitation voltage and a second current 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.”; Examiner notes reference teaches multiple electrode configuration with sequential, repetitive measurements. )
RAHMAN does not teach:
(Claims 1 and 18) determining the value indicative of the impedance of the suspension by relating the first impedance measurement value of the suspension and the second impedance measurement value of the suspension,
(Claims 1 and 18) wherein determining the value indicative of the impedance of the suspension 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 of the suspension and the second impedance measurement value of the suspension, the correction function representing the transmission behavior of the measurement arrangement,
(Claims 1 and 18) wherein the relating of the first impedance measurement value of the suspension and the second impedance measurement value 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 teaches:
(Claims 1 and 18) determining the value indicative of the impedance of the suspension by relating the first impedance measurement value of the suspension and the second impedance measurement value of the suspension, (PELSTER, 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 “relating” 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.)
(Claims 1 and 18) wherein determining the value indicative of the impedance of the suspension 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 of the suspension and the second impedance measurement value of the suspension, 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].)
(Claims 1 and 18) wherein the relating of the first impedance measurement value of the suspension and the second impedance measurement value 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 modify RAHMAN to include the steps as shown above of determining the value indicative of the impedance of the suspension by relating the first impedance measurement value of the suspension and the second impedance measurement value of the suspension, wherein determining the value indicative of the impedance of the suspension 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 of the suspension and the second impedance measurement value of the suspension, the correction function representing the transmission behavior of the measurement arrangement, and wherein the relating of the first impedance measurement value of the suspension and the second impedance measurement value of the suspension is carried out according to the formula as shown above, with variable quantities defined as shown above, as taught by PELSTER because it would provide a means of isolating the suspension properties while minimizing the impact of stray capacitance resulting from electrode configuration and would be reasonably expected to improve accuracy and reliability of resulting impedance value. Combining the techniques taught by PELSTER with the method as taught by RAHMAN would be recognized by one of ordinary skill in the art as a way to reduce uncertainty in an impedance value of the matter between measurement electrodes, independent of specific material or application. One of ordinary skill would be motivated to combine the multiple electrode method for impedance measurements as disclosed by RAHMAN, with the more 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, by eliminating stray electric field effects due to capacitive properties of electrode. Further, this modification would not require significant alterations to the system disclosed by RAHMAN, meaning that implementation would be convenient way to extract intrinsic impedance of the material from the impedance properties of the actual measurement setup taught by RAHMAN. Further, including the mathematical approach taught by PELTZER would be seen as an advantage based on a generally known equation and process derived from the fundamental consideration of the electrical properties as measured in an electrochemical impedance spectroscopy system using basic principles and definitions of impedance.
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 14, RAHMAN, in view of PELSTER, teaches the limitations of claim 1.
RAHMAN further teaches:
determining a third impedance measurement value of the suspension 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, as modified by PELSTER and taught above, does not teach:
and determining the value indicative of the impedance of the suspension by relating 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 and 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 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”)
Claim 7 is 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 7, RAHMAN, in view of PELSTER, teaches the limitations of claim 1.
RAHMAN, as modified by PELSTER and taught above, does not teach:
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:
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 further modify RAHMAN, as modified by PELSTER and 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, as taught by PELSTER because it would be understood that voltage measurements are required to determine any spurious 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 and 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 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 and taught above, to include measuring the first voltage and measuring the second voltage are performed substantially simultaneously, as taught by 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, as modified by PELSTER and taught above, 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, as taught by 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 and 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, as taught by 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 and 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, as taught 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, (RAHMAN, as above, parallel limitation discussed in Claim 1.)
RAHMAN, as modified by PELSTER and taught above, 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 and taught above, to include 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, as taught 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 and 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 relating 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, (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 and 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, as taught by 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 and 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 and 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 and 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, 43 are rejected under 35 U.S.C. 103 as being unpatentable over TODD (EP 2405263 B1) in view of PELSTER.
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 of the suspension on the basis of the excitation current and the first voltage, to determine a second impedance measurement value of the suspension on the basis of the excitation current and the second voltage, and to determine the value indicative of the impedance of the suspension by relating the first impedance measurement value of the suspension and the second impedance measurement value of the suspension,
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,
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
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 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 measurements 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])
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
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 modify TODD to include the steps as described above of:
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, and
wherein the data processing device is configured to determine the value indicative of the impedance of the suspension according to the formula as shown above, with variable quantities defined as shown above, as taught by 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. One of ordinary skill would understand the advantage of using the method of PELSTER to isolate suspension properties while minimizing the impact of stray capacitance resulting from electrode configuration and would be reasonably expected to improve accuracy and reliability of resulting impedance value. Combining the techniques taught by TODD and PELSTER would be motivated by relying on more 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.
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])
Allowable Subject Matter
Claims 15, 16 (with dependence directly to Claim 14 and indirectly to claim 1), Claim 20 (with dependence directly to Claim 19 and indirectly to claim 1) and Claim 40 (with dependence directly to claim 24) are objected to as being dependent upon a rejected base claim but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter:
Specifically, regarding Claim 15, Examiner finds amendment to remove the portion of the claim that was discovered and cited in prior art in previous office action results in a limitation which is not found in best discovered prior art. Claim 15 as currently amended, recites:
“wherein determining the value indicative of the impedance of the suspension comprises determining a first difference between the first adjusted impedance value and the second adjusted impedance value and determining a second difference between the first adjusted impedance value and a third adjusted impedance value and determining a third difference between the second adjusted impedance value and the third adjusted impedance value, wherein the first adjusted impedance value, the second adjusted impedance value and the third adjusted impedance value are obtained by applying the correction function to the first impedance measurement value, the second impedance measurement value and the third impedance measurement value.”
As noted in previous office action, and noted below for previously identified allowable subject matter, RAHMAN can be relied upon to teach a multiple electrode system, FIGs 1,2, with § 2.2. However, the amended claim language recites a sequential set of measurements and determined values, “first”, “second”, and “third” “adjusted impedance value”, where values are determined as specifically recited differences upon application of the correction function before determination of difference. This specific order of steps and determination of values is not recited either individually or in an obvious combination of discovered prior art made available on or before the effective filing date of the claimed invention.
As noted in previous office action 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
3
denotes the third impedance measurement value,
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. Examiner notes that even with amendments, which are understood as simply removing previously defined variables, the limitation is not found in prior art.
Regarding Claim 20, which recites “method for determining a value indicative of the impedance of a suspension is performed for between 10 and 40 different excitation frequencies, and/or wherein the different excitation frequencies are from a frequency range from 50 kHz to 20 MHz.” The specificity of the number of frequencies applied and the range of frequencies is not found in prior art. The technical field would be known to use a variation in frequency and a range of frequency values in an impedance spectroscopy application, such as that taught by RAHMAN, but the specific number or frequencies and specified range of frequencies as claimed was not found in prior art, taught by individual references or using references in a proper obvious combination. Regarding Claim 40, the closest 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”. The specific limits on the capacitance value as claimed was not found. While one of ordinary skill would understand the necessity and role of a transformer in an oscillator circuit integrated within an 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.
For the reasons and rationale as described above, limitations of Claims 15, 16, 20 and 40 renders these claim allowable over prior art, if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
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.
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/TONI D SAUNCY/Examiner, Art Unit 2857
/Catherine T. Rastovski/Supervisory Primary Examiner, Art Unit 2857
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