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 .
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION. —The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 19-36 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 19 recites the limitation “a sample”. It is unclear what is meant by a sample. For the purpose of a compact prosecution, we have interpreted the limitation to mean a sample with HMI.
Claim Rejections - 35 USC § 101
Claims 19-36 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
Specifically, representative Claim 1 recites:
“A system comprising an apparatus for measuring the concentration and presence of heavy metal ions (HMI) in a sample by electrochemical impedance spectroscopy (EIS), comprising: a. a first module including a communication unit and configured to provide voltage and electrical currents in a first frequency band and to measure the impedance of the sample in the first frequency band, b. at least a second module including a communication unit and configured to provide voltage and electrical currents in a second frequency band different from the first band and to measure impedance in the second band, and c. a housing in which are arranged a system controller connected to the communication modules of the first and second module, a data processor, a power module, one or more environmental sensors, and a heating/cooling unit connected to a supply unit for providing cooling/heating fluid, the data processor being configured to combine the measurements from the first frequency band with measurements in the second frequency band in said data processor, to calculate the concentration of a certain HMI and to establish in real time or near real time, wherein a priori knowledge is used by the data processor in the combination, and the a priori knowledge is related to measurements of certain samples comprising HMIs at earlier times, wherein HMIs are dissolved in a known solvent, such as water, and the concentrations are measured at a peak and a valley marking point in the Bode plot of the frequency bands to detect HMI in the known solvent.”
The claim limitations in the abstract idea have been highlighted in bold above; the remaining limitations are “additional element”.
Under the Step 1 of the eligibility analysis, we determine whether the claims are to a statutory category by considering whether the claimed subject matter falls within the four statutory categories of patentable subject matter identified by 35 U.S.C. 101: Process, machine, manufacture, or composition of matter. The above claim is considered to be in a statutory category (process).
Under the Step 2A, Prong One, we consider whether the claim recites a judicial exception (abstract idea). In the above claim, the highlighted portion constitutes an abstract idea because, under a broadest reasonable interpretation, it recites limitations that fall into/recite an abstract idea exceptions. Specifically, under the 2019 Revised Patent Subject matter Eligibility Guidance, it falls into the groupings of subject matter when recited as such in a claim limitation that falls into the grouping of subject matter when recited as such in a claim limitation, that covers mathematical concepts - mathematical relationships, mathematical formulas or equations, mathematical calculations.
The steps of “to calculate the concentration of a certain HMI and to establish in real time or near real time, wherein a priori knowledge is used by the data processor in the combination, and the a priori knowledge is related to measurements of certain samples comprising HMIs at earlier times, wherein HMIs are dissolved in a known solvent, such as water” are treated as belonging to mathematical grouping.
Next, under the Step 2A, Prong Two, we consider whether the claim that recites a judicial exception is integrated into a practical application.
In this step, we evaluate whether the claim recites additional elements that
integrate the exception into a practical application of that exception.
The above claims comprise the following additional elements:
Claim 19: A system comprising an apparatus for measuring the concentration and presence of heavy metal ions (HMI) in a sample by electrochemical impedance spectroscopy (EIS), comprising: a. a first module including a communication unit and configured to provide voltage and electrical currents in a first frequency band and to measure the impedance of the sample in the first frequency band, b. at least a second module including a communication unit and configured to provide voltage and electrical currents in a second frequency band different from the first band and to measure impedance in the second band, and c. a housing in which are arranged a system controller connected to the communication modules of the first and second module, a data processor, a power module, one or more environmental sensors, and a heating/cooling unit connected to a supply unit for providing cooling/heating fluid, the data processor being configured to combine the measurements from the first frequency band with measurements in the second frequency band in said data processor… and the concentrations are measured at a peak and a valley marking point in the Bode plot of the frequency bands to detect HMI in the known solvent.
Claim 31: A method for measuring the concentration and presence of heavy metal ions (HMI) in a sample by electrochemical impedance spectroscopy (EIS), wherein: a. the impedance of the sample is measured in a first frequency band of a first module including a communication unit and configured to provide voltage and electrical currents in the first frequency band, b. the impedance is measured at least in a second frequency band of least a second module including a communication unit and configured to provide voltage and electrical currents in a second frequency band different from the first band, and the measurements from the first frequency band are combined with measurements in the second frequency band in a data processor, wherein a priori knowledge is used by the data processor in the combination, … and the a priori knowledge is related to measurements of certain samples comprising HMIs at earlier times, wherein HMIs are dissolved in a known solvent, such as water, and the concentrations are measured at a peak and a valley marking point in the Bode plot of the frequency bands to detect HMI in the known solvent, and c. the data processor is arranged in a housing, in which are also arranged a system controller connected to the communication modules of the first and second module, a data processor, a power module, one or more environmental sensors, and a heating/cooling unit connected to a supply unit for providing cooling/heating fluid.
The above steps of a system comprising an apparatus for measuring the concentration and presence of heavy metal ions (HMI) in a sample by electrochemical impedance spectroscopy (EIS), comprising: a. a first module including a communication unit and configured to provide voltage and electrical currents in a first frequency band and to measure the impedance of the sample in the first frequency band, b. at least a second module including a communication unit and configured to provide voltage and electrical currents in a second frequency band different from the first band and to measure impedance in the second band, and c. a housing in which are arranged a system controller connected to the communication modules of the first and second module, a data processor, a power module, one or more environmental sensors, and a heating/cooling unit connected to a supply unit for providing cooling/heating fluid, the data processor being configured to combine the measurements from the first frequency band with measurements in the second frequency band in said data processor… and the concentrations are measured at a peak and a valley marking point in the Bode plot of the frequency bands to detect HMI in the known solvent are generically recited, represent mere data gathering steps (insignificant extra-solution activity), and outputting results necessary to execute the abstract idea.
The additional elements in Claim 31 such as a data processor is an example of generic computer equipment (components) that is generally recited and, therefore, is not qualified as a particular machine.
Therefore, the claims are directed to a judicial exception and require further analysis under the Step 2B.
However, the above claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception (Step 2B analysis) because these additional elements/steps are well-understood and conventional in the relevant art based on the prior art of record including references in the submitted IDS (6/29/2023) by the Applicant (Prasad and Drbal).
The independent claims, therefore, are not patent eligible.
With regards to the dependent claims, claims 20-30 and 32-36 provide additional features/steps which are either part of an expanded abstract idea of the independent claims (additionally comprising mathematical/mental/organizing human activity process steps (Claims 20-30 and 32-36) or adding additional elements/steps that are not meaningful as they are recited in generality and/or not qualified as particular machine/ and/or eligible transformation and, therefore, do not reflect a practical application as well as not qualified for “significantly more” based on prior art of record.
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 19, 21-22, 24, 25-29, 31, and 33-35 are rejected under 35 U.S.C. 103 as being unpatentable Prasad et al. (US20150276637), hereinafter referred to as ‘Prasad’ and in further view of Drbal et al. (US20160018347), hereinafter referred to as ‘Drbal’ and Lee et al. (KR101793922), hereinafter referred to as ‘Lee’.
Regarding Claim 19, Prasad discloses a system comprising an apparatus for measuring the concentration and presence of heavy metal ions (HMI) in a sample by electrochemical impedance spectroscopy (EIS), comprising (Exemplary embodiments of the claimed invention include apparatus and methods for performing impedance spectroscopy with a handheld potentiometer [0009]; … using the measured impedance and associated phase angle at different frequencies to detect multiple target analytes or calculate concentrations of target analytes by use of a standard calibration curve [0010]; The handheld potentiostats and porous nanotextured conformal circuits disclosed herein may be used separately or in combination to detect and/or quantify a target analyte. In some embodiments, disclosed is a method of detecting a target analyte comprising spotting a sample on a disclosed conformal analyte sensor circuit… In some embodiments, the source circuit is a current source. In some embodiments, the sample contains 1-10 μl of a fluid. In some embodiments, the target analyte is a protein, DNA, RNA, SNP, small molecules, pathogens heavy metal ions, or physiological ions. In some embodiments, the sample is not labeled [0040]): a. a first module including a communication unit and configured to provide voltage and electrical currents in a first frequency band and to measure the impedance of the sample in the first frequency band , b. at least a second module including a communication unit and configured to provide voltage and electrical currents in a second frequency band different from the first band and to measure impedance in the second band (Exemplary embodiments include a method of detecting or quantifying a target analyte in a sample using a handheld measuring device and a conformal analyte sensor circuit comprising the steps of: (a) placing a sample containing multiple target analytes on a conformal substrate having a sensor circuit comprising a first electrode, a second electrode, a third electrode, a fourth electrode, a fifth electrode and a sixth electrode; (b) applying a first alternating input electric voltage between the first electrode and the second electrode at a first phase angle; (c) applying a second alternating input electric voltage between the third electrode and the second electrode at a second phase angle, wherein the first phase angle and the second phase angle are separated by a first constant delta phase angle; (d) measuring a first output current at different frequencies over a first range of frequencies and varying phase angles over a first range of phase angles; (e) amplifying the first output current flowing from the first electrode and from the third electrode through the second electrode using a programmable gain amplifier; (f) sectioning a first electrical double layer into a plurality of planes in three dimensional space, wherein the first electrical double layer is proximal to a surface of first electrode, a surface of the second electrode, and a surface of the third electrode; (g) varying the first phase angle of the first input electric voltage and the second phase angle of the second input electric voltage over the first range of phase angles; (h) identifying the first phase angle and the second phase angle at which a first maximum impedance change occurs; (i) measuring the impedance identified at the first phase angle and the second phase angle; (j) using the measured impedance at different frequencies to detect a first target analyte or calculate a concentration of the first target analyte by use of a standard calibration curve [0015]; The first operation of the microcontroller is providing user interface support through an LCD display 104. The serial peripheral interface SPI2 is used to communicate information processed in the microcontroller 100 to the LCD display 104 [0105]), and c. a housing in which are arranged a system controller connected to the communication modules of the first and second module, a data processor, a power module, one or more environmental sensors (Exemplary embodiments include a handheld device for measuring a target analyte comprising: (a) a programmable gain amplifier configured to be operably coupled to a first electrode, a second electrode, and a third electrode; (b) a programmable microcontroller operably coupled to the programmable gain amplifier, the first electrode, the second electrode, and the third electrode; where the programmable microcontroller is operable to apply a first alternating input electric voltage between the first electrode and the second electrode; the programmable microcontroller is operable to apply a second alternating input electric voltage between the third electrode and the second electrode; the programmable gain amplifier is operable to amplify an alternating output current flowing from the first electrode and from the third electrode through the second electrode; the programmable microcontroller is operable to calculate an impedance by comparing the first input electric voltage and the second input electric voltage to the measured output current; and the programmable microcontroller is operable to calculate a target analyte concentration from the calculated impedance [0025]), the data processor being configured to combine the measurements from the first frequency band with measurements in the second frequency band in said data processor, to calculate the concentration of a certain HMI and to establish in real time or near real time (Exemplary embodiments include a method of detecting or quantifying multiple target analytes in a sample using a handheld measuring device and a conformal analyte sensor circuit comprising the steps of: … (h) identifying the first phase angle and the second phase angle at which a maximum impedance change occurs; (i) measuring the impedance identified at the first phase angle and the second phase angle; and (j) using the measured impedance and associated phase angle at different frequencies to detect multiple target analytes or calculate concentrations of target analytes, i.e., certain HMI, by use of a standard calibration curve [0010]), wherein a priori knowledge is used by the data processor in the combination, and the a priori knowledge is related to measurements of certain samples comprising HMIs at earlier times (FIG. 10 is another Bode plot representing phase change in the impedance versus the frequency of the applied signal for a solution … exhibit unique impedance phase profiles that demonstrate the ability to distinguish multiple biomarkers in solution based upon spectroscopic analysis [0149]), the Bode plot of the frequency bands to detect HMI in the known solvent (FIG. 10 is another Bode plot representing phase change in the impedance versus the frequency of the applied signal for a solution … exhibit unique impedance phase profiles that demonstrate the ability to distinguish multiple biomarkers in solution based upon spectroscopic analysis [0149]).
However, Prasad does not explicitly disclose a heating/cooling unit connected to a supply unit for providing cooling/heating fluid, the data processor being configured to combine the measurements from the first frequency band with measurements in the second frequency band in said data processor, to calculate the concentration of a certain HMI and to establish in real time or near real time, wherein HMIs are dissolved in a known solvent, such as water, and the concentrations are measured at a peak and a valley marking point in the Bode plot of the frequency bands to detect HMI in the known solvent.
Nevertheless, Drbal discloses a heating/cooling unit connected to a supply unit for providing cooling/heating fluid (In some variations the sensor includes a flow sensor. The flow sensor may be a hot wire anemometer. The sensor may also include a temperature sensor. In some variations the sensor includes a heating element to regulate the temperature of fluid being sensed by the sensor [0213]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Prasad in view of Drbal to include a heating/cooling unit connected to a supply unit for providing cooling/heating fluid to regulate the temperature of fluid being sensed by the sensor and to improve efficiency, performance, and longevity of the apparatus.
However, the combination does not explicitly disclose the data processor being configured to combine the measurements from the first frequency band with measurements in the second frequency band in said data processor, to calculate the concentration of a certain HMI and to establish in real time or near real time, wherein a priori knowledge is used by the data processor in the combination, and the a priori knowledge is related to measurements of certain samples comprising HMIs at earlier times, wherein HMIs are dissolved in a known solvent, such as water, and the concentrations are measured at a peak and a valley marking point in the Bode plot of the frequency bands to detect HMI in the known solvent.
Nevertheless, Lee discloses HMIs are dissolved in a known solvent, such as water, and the concentrations are measured at a peak and a valley marking point in the Bode plot of the frequency bands to detect HMI in the known solvent (Prepare target water containing dissolved inorganic ions. The above target water may be seawater, wastewater, tap water, purified water, river water, effluent, etc., and the inorganic ions dissolved in the target water refer to cations such as heavy metal ions, excluding anionic ions [0057]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Prasad and Drbal, in view of Lee to include HMIs dissolved in a known solvent, such as water, and the concentrations are measured at a peak and a valley marking point in the Bode plot of the frequency bands to detect HMI in the known solvent to identify data related to the dissolved HMIs while detecting and quantifying the HMIs and to improve statistical analysis of impedance responses.
Regarding Claim 21, Prasad, Drbal, and Lee disclose the claimed invention discussed in claim 19.
Prasad discloses the sample comprises heavy metal ions dissolved in a bipolar solvent, such as water, and wherein the first frequency band is below 50 Hz and the second frequency band is between 1kHz and 1MHz (as discussed above).
However. Prasad does not explicitly disclose the sample comprises heavy metal ions dissolved in a bipolar solvent, such as water, and wherein the first frequency band is below 50 Hz and the second frequency band is between 1kHz and 1MHz.
Nevertheless, Drbal discloses the sample comprises heavy metal ions dissolved in a bipolar solvent, such as water, and wherein the first frequency band is below 50 Hz and the second frequency band is between 1kHz and 1MHz (The signal generator may be configured to provide electrical excitation at a plurality of frequencies including a low frequency range. The low frequency range may mean from less than about 1 Hz, less than about 100 milliHertz, less than about 10 milliHertz, etc. In some variations the applied frequency range may extend to a relatively high frequency range as well (e.g., greater than about 1 KHz, 10 KHz, 100 KHz, 1 MHz, 10 MHz, etc.) [0218]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Prasad in view of Drbal to the first frequency band is below 50 Hz and the second frequency band is between 1kHz and 1MHz to provide electrical excitation at a plurality of frequencies to obtain a plurality of complex impedance measurements (Drbal [0196]) and improve statistical analysis of the apparatus.
However, the combination does not explicitly disclose the sample comprises heavy metal ions dissolved in a bipolar solvent, such as water, and wherein the first frequency band is below 50 Hz and the second frequency band is between 1kHz and 1MHz.
Nevertheless, Lee discloses the sample comprises heavy metal ions dissolved in a bipolar solvent, such as water (as discussed above).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Prasad and Drbal, in view of Lee to the sample comprises heavy metal ions dissolved in a bipolar solvent, such as water, and wherein the first frequency band is below 50 Hz and the second frequency band is between 1kHz and 1MHz to provide electrical excitation at a plurality of frequencies to obtain a plurality of complex impedance measurements (Drbal [0196]) and improve statistical analysis of the heavy metal ions dissolved in a bipolar solvent.
Regarding Claim 22, Prasad, Drbal, and Lee disclose the claimed invention discussed in claim 21.
Prasad discloses the heavy metals include Mercury (Hg), Cadmium (Cd), Arsenic (As), Chromium (Cr), Lead (Pb), Zinc (Zn), Copper (Cu), Iron (Fe), Silver (Ag) and Nickel (Ni) (A particular type of chemical or biological agent is a toxin. Toxins can be biological, i.e., produced by an organism. These include toxins that may be used in biological warfare or terrorism, including ricin, anthrax toxin, and botulism toxin. Other toxins are pesticides (insecticides, herbicides; e.g., organophosphates), industrial contaminants (heavy metals, such as cadmium, thallium, copper, zinc, selenium, antimony, nickel, chromium, arsenic, mercury or lead; complex hydrocarbons, include PCBs, and petroleum byproducts; asbestos), and chemical warfare reagents (sarin, soman, cyclosarin, VX, VG, GV, phosgene oxime, nitrogen mustard, sulfur mustard and cyanogen chloride). [0055]).
Regarding Claim 24, Prasad, Drbal, and Lee disclose the claimed invention discussed in claim 19.
Prasad discloses the EIS module and the apparatus being provided with memory for storing data from earlier measurements, either locally or, preferably, remotely in a network with on-line access, and preferably provided with computer power for AI, or deep learning (The claimed system may perform non-Faradaic electrochemical impedance spectroscopy (EIS) by testing samples without using a redox electrode [0046]; The microcontroller then compares the frequency at which the maximum impedance change occurred to the reference frequency point stored in memory for the specific analyte being tested [0121]).
However, Prasad does not explicitly disclose each module comprises a board provided with a temperature sensor connected to a secondary heating/cooling element for finely tuning the temperature control of the EIS module and the apparatus being provided with memory for storing data from earlier measurements, either locally or, preferably, remotely in a network with on-line access, and preferably provided with computer power for AI, or deep learning.
Nevertheless, Drbal discloses each module comprises a board provided with a temperature sensor connected to a secondary heating/cooling element for finely tuning the temperature control (In some variations the sensor includes a flow sensor. The flow sensor may be a hot wire anemometer. The sensor may also include a temperature sensor. In some variations the sensor includes a heating element to regulate the temperature of fluid being sensed by the sensor. [0213]; In general, any of the sensors described herein may include one or more temperature control elements (including heating elements) for controlling the temperature of the sample [0342]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Prasad and Drbal, in view of Lee to each module comprises a board provided with a temperature sensor connected to include a secondary heating/cooling element for finely tuning the temperature control of the EIS module to provide precise temperature adjustments and rapid temperature corrections while improving accuracy of the measurements.
Regarding Claim 25, Prasad, Drbal, and Lee disclose the claimed invention discussed in claim 19.
Prasad discloses a working electrode, a counter electrode and a reference electrode (Particular embodiments include an analyte sensor circuit comprising: a substrate having a surface comprising a conductive material (with or without textured porosity) situated on the surface in a circuit design, thereby creating a circuit comprising a first electrode, a second electrode and a third electrode [0011]).
Regarding Claim 26, Prasad, Drbal, and Lee disclose the claimed invention discussed in claim 25.
Prasad discloses the three electrodes (as discussed above).
However, Prasad does not explicitly disclose the three electrodes are aligned or in which the three electrodes are forming a triangle, in which the working electrode and the counter-electrode are preferably made of platinum.
Nevertheless, Drbal discloses the counter-electrode are preferably made of platinum (Electrode pairs composed of different electrically conductive metals (e.g. silver, gold, platinum, titanium, etc.) [0197]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Prasad and Drbal, in view of Lee to the three electrodes are aligned or in which the three electrodes are forming a triangle, in which the working electrode and the counter-electrode are preferably made of platinum to provide excellent electrical conductivity, high resistance to corrosion, to ensure that the electrochemical process is controlled by the working electrode and to improve accuracy of measurements.
Regarding Claim 27, Prasad, Drbal, and Lee disclose the claimed invention discussed in claim 19.
Prasad discloses the three electrodes (as discussed above).
However, Prasad does not explicitly disclose the three electrodes are held in steady positions the one in respect to the other through being moulded in an acrylic resin holder, and the reference electrode extends through the acrylic resin holder in a hollow tube of larger diameter.
Nevertheless, Drbal discloses the three electrodes are held in steady positions the one in respect to the other through, and the reference electrode extends through the holder in a hollow tube of larger diameter (FIGS. 22A and 22B illustrate another variation of a tubular mount that may be used in-line or static (if one end is closed off). The sensor of this example includes both a low ionic strength electrode region 2201 and high ionic strength single pads 2203. If designed with symmetric ring or other symmetric structure contacts, the sensor tube assembly can be installed into a system without requiring rotational alignment. FIGS. 23A and 23B illustrate another variation of a cylindrical mount for one or more sensors 2301, 2303 that may be used with an over molded outer sleeve or housing 2307 [0308]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Prasad and Drbal, in view of Lee to include the three electrodes are held in steady positions the one in respect to the other through being moulded in an acrylic resin holder, and the reference electrode extends through the acrylic resin holder in a hollow tube of larger diameter to provide clear, organized , and safe storage to prevent damage and loss and improve stability of the apparatus.
Regarding Claim 28, Prasad, Drbal, and Lee disclose the claimed invention discussed in claim 19.
Prasad discloses the a priori knowledge is stored in a library and the measurements in the first frequency band are compared with data in the library, whereafter it is decided which measurements are made in the second frequency band, if necessary (The microcontroller then compares the frequency at which the maximum impedance change occurred to the reference frequency point stored in memory for the specific analyte being tested. The microcontroller estimates the concentration of the tested analyte by applying the same equation used in calibration [0121]).
Regarding Claim 29, Prasad, Drbal, and Lee disclose the claimed invention discussed in claim 28.
Prasad discloses an AI processor and an AI algorithm connected to the library, forming a processing unit (In certain embodiments, the scanning mechanism is adaptive as it compares the current measurement with the previously measured impedance at the prior frequency or phase step. In particular embodiments, from this comparison an algorithm can be applied to interpret if there is a variation or change to the measured signal which is two standard deviations from the previous measurement [0088]).
Regarding Claim 31, Prasad discloses a method for measuring the concentration and presence of heavy metal ions (HMI) in a sample by electrochemical impedance spectroscopy (EIS) (Exemplary embodiments of the claimed invention include apparatus and methods for performing impedance spectroscopy with a handheld potentiometer [0009]; … using the measured impedance and associated phase angle at different frequencies to detect multiple target analytes or calculate concentrations of target analytes by use of a standard calibration curve [0010]; The handheld potentiostats and porous nanotextured conformal circuits disclosed herein may be used separately or in combination to detect and/or quantify a target analyte. In some embodiments, disclosed is a method of detecting a target analyte comprising spotting a sample on a disclosed conformal analyte sensor circuit… In some embodiments, the source circuit is a current source. In some embodiments, the sample contains 1-10 μl of a fluid. In some embodiments, the target analyte is a protein, DNA, RNA, SNP, small molecules, pathogens heavy metal ions, or physiological ions. In some embodiments, the sample is not labeled [0040]): wherein: a. the impedance of the sample is measured in a first frequency band of a first module including a communication unit and configured to provide voltage and electrical currents in the first frequency band, b. the impedance is measured at least in a second frequency band of least a second module including a communication unit and configured to provide voltage and electrical currents in a second frequency band different from the first band and the measurements from the first frequency band are combined with measurements in the second frequency band in a data processor (Exemplary embodiments include a method of detecting or quantifying a target analyte in a sample using a handheld measuring device and a conformal analyte sensor circuit comprising the steps of: (a) placing a sample containing multiple target analytes on a conformal substrate having a sensor circuit comprising a first electrode, a second electrode, a third electrode, a fourth electrode, a fifth electrode and a sixth electrode; (b) applying a first alternating input electric voltage between the first electrode and the second electrode at a first phase angle; (c) applying a second alternating input electric voltage between the third electrode and the second electrode at a second phase angle, wherein the first phase angle and the second phase angle are separated by a first constant delta phase angle; (d) measuring a first output current at different frequencies over a first range of frequencies and varying phase angles over a first range of phase angles; (e) amplifying the first output current flowing from the first electrode and from the third electrode through the second electrode using a programmable gain amplifier; (f) sectioning a first electrical double layer into a plurality of planes in three dimensional space, wherein the first electrical double layer is proximal to a surface of first electrode, a surface of the second electrode, and a surface of the third electrode; (g) varying the first phase angle of the first input electric voltage and the second phase angle of the second input electric voltage over the first range of phase angles; (h) identifying the first phase angle and the second phase angle at which a first maximum impedance change occurs; (i) measuring the impedance identified at the first phase angle and the second phase angle; (j) using the measured impedance at different frequencies to detect a first target analyte or calculate a concentration of the first target analyte by use of a standard calibration curve [0015]; The first operation of the microcontroller is providing user interface support through an LCD display 104. The serial peripheral interface SPI2 is used to communicate information processed in the microcontroller 100 to the LCD display 104 [0105]), to calculate the concentration of a certain HMI and to establish in real time near real time (Exemplary embodiments include a method of detecting or quantifying multiple target analytes in a sample using a handheld measuring device and a conformal analyte sensor circuit comprising the steps of: … (h) identifying the first phase angle and the second phase angle at which a maximum impedance change occurs; (i) measuring the impedance identified at the first phase angle and the second phase angle; and (j) using the measured impedance and associated phase angle at different frequencies to detect multiple target analytes or calculate concentrations of target analytes, i.e., certain HMI, by use of a standard calibration curve [0010]), wherein a priori knowledge is used by the data processor in the combination, and the a priori knowledge is related to measurements of certain samples comprising HMIs at earlier times (FIG. 10 is another Bode plot representing phase change in the impedance versus the frequency of the applied signal for a solution … exhibit unique impedance phase profiles that demonstrate the ability to distinguish multiple biomarkers in solution based upon spectroscopic analysis [0149]), marking point in the Bode plot of the frequency bands to detect HMI in the known solvent (FIG. 10 is another Bode plot representing phase change in the impedance versus the frequency of the applied signal for a solution … exhibit unique impedance phase profiles that demonstrate the ability to distinguish multiple biomarkers in solution based upon spectroscopic analysis [0149]), and c. the data processor is arranged in a housing, in which are also arranged a system controller connected to the communication modules of the first and second module, a data processor, a power module, one or more environmental sensors (Exemplary embodiments include a handheld device for measuring a target analyte comprising: (a) a programmable gain amplifier configured to be operably coupled to a first electrode, a second electrode, and a third electrode; (b) a programmable microcontroller operably coupled to the programmable gain amplifier, the first electrode, the second electrode, and the third electrode; where the programmable microcontroller is operable to apply a first alternating input electric voltage between the first electrode and the second electrode; the programmable microcontroller is operable to apply a second alternating input electric voltage between the third electrode and the second electrode; the programmable gain amplifier is operable to amplify an alternating output current flowing from the first electrode and from the third electrode through the second electrode; the programmable microcontroller is operable to calculate an impedance by comparing the first input electric voltage and the second input electric voltage to the measured output current; and the programmable microcontroller is operable to calculate a target analyte concentration from the calculated impedance [0025]).
However, Prasad does not explicitly disclose a heating/cooling unit connected to a supply unit for providing cooling/heating fluid and wherein HMIs are dissolved in a known solvent, such as water, and the concentrations are measured at a peak and a valley marking point in the Bode plot of the frequency bands to detect HMI in the known solvent.
Nevertheless, Drbal discloses a heating/cooling unit connected to a supply unit for providing cooling/heating fluid (In some variations the sensor includes a flow sensor. The flow sensor may be a hot wire anemometer. The sensor may also include a temperature sensor. In some variations the sensor includes a heating element to regulate the temperature of fluid being sensed by the sensor [0213]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Prasad in view of Drbal to include a heating/cooling unit connected to a supply unit for providing cooling/heating fluid to regulate the temperature of fluid being sensed by the sensor and to improve efficiency, performance, and longevity of the apparatus.
However, the combination does not explicitly disclose wherein HMIs are dissolved in a known solvent, such as water, and the concentrations are measured at a peak and a valley marking point in the Bode plot of the frequency bands to detect HMI in the known solvent.
Nevertheless, Lee discloses HMIs are dissolved in a known solvent, such as water (Prepare target water containing dissolved inorganic ions. The above target water may be seawater, wastewater, tap water, purified water, river water, effluent, etc., and the inorganic ions dissolved in the target water refer to cations such as heavy metal ions, excluding anionic ions [0057]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Prasad and Drbal, in view of Lee to include HMIs dissolved in a known solvent, such as water, and the concentrations are measured at a peak and a valley marking point in the Bode plot of the frequency bands to detect HMI in the known solvent to identify data related to the dissolved HMIs while detecting and quantifying the HMIs and to improve statistical analysis of impedance responses.
Regarding Claim 33, Prasad, Drbal, and Lee disclose the claimed invention discussed in claim 31.
However, Prasad does not explicitly disclose rinsing takes place after each or a number of measurements.
Nevertheless, Drbal discloses rinsing takes place after each or a number of measurements (Any of the systems described herein may also include a rinse module connected to a source of rinsate to rinse the sample chamber after delivery of a liquid (e.g., liquid drug waste) [0237]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Prasad and Drbal, in view of Lee to include rinsing takes place after each or a number of measurements to avoid carryover contamination and to improve measurement procedures and statistical analysis of impedance responses.
Regarding Claim 34, Prasad, Drbal, and Lee disclose the claimed invention discussed in claim 31.
Prasad discloses the sample comprises heavy metal ions dissolved in a bipolar solvent, such as water, and wherein the first frequency band is below 50 Hz and the second frequency band is between 1kHz and 1MHz (as discussed above).
However. Prasad does not explicitly disclose the sample comprises heavy metal ions dissolved in a bipolar solvent, such as water, and wherein the first frequency band is below 50 Hz and the second frequency band is between 1kHz and 1MHz.
Nevertheless, Drbal discloses the sample comprises heavy metal ions dissolved in a bipolar solvent, such as water, and wherein the first frequency band is below 50 Hz and the second frequency band is between 1kHz and 1MHz (The signal generator may be configured to provide electrical excitation at a plurality of frequencies including a low frequency range. The low frequency range may mean from less than about 1 Hz, less than about 100 milliHertz, less than about 10 milliHertz, etc. In some variations the applied frequency range may extend to a relatively high frequency range as well (e.g., greater than about 1 KHz, 10 KHz, 100 KHz, 1 MHz, 10 MHz, etc.) [0218]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Prasad in view of Drbal to the first frequency band is below 50 Hz and the second frequency band is between 1kHz and 1MHz to provide electrical excitation at a plurality of frequencies to obtain a plurality of complex impedance measurements (Drbal [0196]) and improve statistical analysis of the apparatus.
However, the combination does not explicitly disclose the sample comprises heavy metal ions dissolved in a bipolar solvent, such as water, and wherein the first frequency band is below 50 Hz and the second frequency band is between 1kHz and 1MHz.
Nevertheless, Lee discloses the sample comprises heavy metal ions dissolved in a bipolar solvent, such as water (as discussed above).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Prasad and Drbal, in view of Lee to the sample comprises heavy metal ions dissolved in a bipolar solvent, such as water, and wherein the first frequency band is below 50 Hz and the second frequency band is between 1kHz and 1MHz to provide electrical excitation at a plurality of frequencies to obtain a plurality of complex impedance measurements (Drbal [0196]) and improve statistical analysis of the heavy metal ions dissolved in a bipolar solvent.
Regarding Claim 35, Prasad, Drbal, and Lee disclose the claimed invention discussed in claim 34.
Prasad discloses the heavy metals include Mercury (Hg), Cadmium (Cd), Arsenic (As), Chromium (Cr), Lead (Pb), Zinc (Zn), Copper (Cu), Iron (Fe), Silver (Ag) and Nickel (Ni) (A particular type of chemical or biological agent is a toxin. Toxins can be biological, i.e., produced by an organism. These include toxins that may be used in biological warfare or terrorism, including ricin, anthrax toxin, and botulism toxin. Other toxins are pesticides (insecticides, herbicides; e.g., organophosphates), industrial contaminants (heavy metals, such as cadmium, thallium, copper, zinc, selenium, antimony, nickel, chromium, arsenic, mercury or lead; complex hydrocarbons, include PCBs, and petroleum byproducts; asbestos), and chemical warfare reagents (sarin, soman, cyclosarin, VX, VG, GV, phosgene oxime, nitrogen mustard, sulfur mustard and cyanogen chloride). [0055]).
Claims 20, 23, and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Prasad, Drbal, and Lee, and further in view of Mohseni et al. (US20150346131) hereinafter referred to as ‘Mohseni’.
Regarding Claim 20, Prasad, Drbal, and Lee disclose the claimed invention discussed in claim 19.
Prasad discloses the frequency bands comprise frequencies from 0.1 Hz- 30 GHz, preferably 10-100 kHz, 100 kHz-1 MHz, and 1 Mhz- 1 GHz, wherein the frequency is preferably swept over the different frequencies (In exemplary embodiments, the first input electric voltage and the second input electric voltage have a frequency between 50 Hz and 5,000 Hz [0019]).
However, Prasad does not explicitly disclose the frequency bands comprise frequencies from 0.1 Hz- 30 GHz, preferably 10-100 kHz, 100 kHz-1 MHz, and 1 Mhz- 1 GHz, wherein the frequency is preferably swept over the different frequencies.
Nevertheless, Mohseni the frequency bands comprise frequencies from 0.1 Hz- 30 GHz, preferably 10-100 kHz, 100 kHz-1 MHz, and 1 Mhz- 1 GHz, wherein the frequency is preferably swept over the different frequencies (The sensor interface system 14 can include a transmitter 22 and a receiver 24. The transmitter 22 can be configured to provide the RF input signal at a desired excitation frequency. The excitation frequency, for example, can be in the microwave range. For instance the transmitter 22 can provide the RF input signal in a range from about 1 MHz to about 100 GHz (e.g., from about 5 MHz to about 10 GHz) [0031]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Prasad, Drbal, and Lee in view of Mohseni to include the frequency bands comprise frequencies from 0.1 Hz- 30 GHz, preferably 10-100 kHz, 100 kHz-1 MHz, and 1 Mhz- 1 GHz, wherein the frequency is preferably swept over the different frequencies to provide electrical excitation at a plurality of frequencies to obtain a plurality of complex impedance measurements (Drbal [0196]) and improve statistical analysis of the heavy metal ions dissolved in a bipolar solvent.
Regarding Claim 23, Prasad, Drbal, and Lee disclose the claimed invention discussed in claim 19.
Prasad discloses comprising modules each module functioning in a different frequency band, ranging from 0.1Hz-1OGHz (as discussed above).
However, Prasad does not explicitly disclose 12 modules each module functioning in a different frequency band, ranging from 0.1Hz-1OGHz.
Nevertheless, Mohseni discloses modules each module functioning in a different frequency band, ranging from 0.1Hz-1OGHz (as discussed above).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Prasad, Drbal, and Lee, in view of Mohseni to 12 modules each module functioning in a different frequency band, ranging from 0.1Hz-1OGHzto provide electrical excitation at a plurality of frequencies to obtain a plurality of complex impedance measurements (Drbal [0196]) and improve statistical analysis of the heavy metal ions dissolved in a bipolar solvent.
Regarding Claim 32, Prasad, Drbal, and Lee disclose the claimed invention discussed in claim 31.
Prasad discloses the frequency bands comprise frequencies from 0.1 Hz- 30 GHz, preferably 10-100 kHz, 100 kHz-1 MHz, and 1 Mhz- 1 GHz, wherein the frequency is preferably swept over the different frequencies (In exemplary embodiments, the first input electric voltage and the second input electric voltage have a frequency between 50 Hz and 5,000 Hz [0019]).
However, Prasad does not explicitly disclose the frequency bands comprise frequencies from 0.1 Hz- 30 GHz, preferably 10-100 kHz, 100 kHz-1 MHz, and 1 Mhz- 1 GHz, wherein the frequency is preferably swept over the different frequencies.
Nevertheless, Mohseni the frequency bands comprise frequencies from 0.1 Hz- 30 GHz, preferably 10-100 kHz, 100 kHz-1 MHz, and 1 Mhz- 1 GHz, wherein the frequency is preferably swept over the different frequencies (The sensor interface system 14 can include a