DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on February 24th, 2026 has been entered.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 01/20/2026 and 02/24/2026 have been considered by the Examiner.
Status of the Claims
Claim 1 has been amended. Claims 3-5 and 12-14 have been previously canceled. Claim 15 has been added. Claims 1-2, 6-11, and 15 are currently examined herein.
Status of the Rejection
All 35 U.S.C. 103 rejections from the previous office action are withdrawn in view of Applicant’s arguments and amendments.
New grounds of 35 U.S.C. 103 are necessitated by Applicant’s arguments and amendments. Claim objections have been added for claims 2 and10 for minor informalities.
Claim Objections
Claims 2 and 10 are objected to because of the following informalities:
Claim 2, please amend “A method for detecting and/or quantifying a metal element in a biological liquid according to claim 1” to “The method according to claim 1”.
Claim 10, please ament “zin c” to “zinc” (remove space).
Appropriate correction is required.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-2, 7-8, 10-11, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Kremplova et al. (Automated Electrochemical Detection of Metal Iron Ions in Erthrocytes from MeLiM Minipigs Suffering from Melanoma, Int. J. Electrochem. Sci., 2012, 7(7), 5893-5909), provided in IDS submitted on 06/09/2025, in view of Cinti et al. (Carbon Black-Modified Electrodes Screen-Printed onto Paper Towel, Waxed Paper, and Parafilm M®, Sensors, 2017, 17, 1-12) and Steen (US 2013/0236977 A1).
Regarding Claim 1, Kremplova teaches a method for detecting and quantifying a metal element in a biological liquid (detection and quantification of compounds of interest, such as iron, in biological samples [abstract]; the biological liquid being supernatant of erythrocytes described in Section 2.5 Preparation of Samples, page 5900]); comprising the steps of
contacting the biological liquid with trifluoroacetic acid (TFA) (supernatant of biological blood plasma sample was combined with trifluoroacetic acid [TFA] solution [Section 2.5 Preparation of Samples, page 5900]);
applying the biological liquid and the TFA to an electroanalytical sensor (diluted sample with TFA was centrifuged, and then supernatant was used for electrochemical determination [Section 2.5 Preparation of Samples, page 5900]; electrodes of the electroanalytical sample are positioned into the sample [second para. page 5894]); and
detecting a current signal which is proportional to an amount of the metal element in the biological liquid by means of the electroanalytical sensor (as illustrated in Figure 5(B), iron concentration is dependent on current signal [page 5905]).
Kremplova is silent on the biological liquid is selected from the group consisting of blood, plasma, and serum, wherein the electroanalytical sensor comprises a support made of cellulose, polyester or a derivative thereof, on which a hydrophobic area delimits a hydrophilic working area, said hydrophilic working area comprising at least one working electrode, one reference electrode and one counter electrode by screen-printing.
Cinti teaches alternative materials for screen-printed electrode manufacturing (abstract), and teaches an electroanalytical sensor (three-electrode screen-printed electrode system [second para. page 3; illustrated in Figure 1, page 3]) comprises a support made of cellulose (support is a cellulose substate such as waxed paper [second para. page 3]), on which a hydrophobic area delimits a hydrophilic working area (as illustrated in photograph Figure 1B, the hydrophobic wax paper area delimits the hydrophilic electrode area composed of conductive ink [second para. page 3]), said hydrophilic working area comprising at least one working electrode, one reference electrode and one counter electrode by screen-printing (three electrode system was manually screen-printed composed of conductive ink [second para. page 3]).
Kremplova and Cinti are considered analogous art to the claimed inventions because they are in the same field of methods to measure metal ions using electroanalytic sensors. It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the electroanalytical sensor of Kremplova to comprise a support made of cellulose, on which a hydrophobic area delimits a hydrophilic working area, said hydrophilic working area comprising at least one working electrode, one reference electrode and one counter electrode by screen-printing, as taught by Cinti, as using a cellulose support serves as a cost-effective alternative sensor manufacturing method (Cinti, [abstract]).
Modified Kremplova is silent on the biological liquid is selected from the group consisting of blood, plasma, and serum.
Steen teaches method for preparing blood samples for analysis, such as peptide analysis [abstract], and teaches the biological liquid is selected from the group consisting of blood, plasma, and serum (sample can be a blood sample, and in some embodiments a plasma sample [para. 0014], and in other embodiments, a serum [para. 0016]; samples are centrifuged and processed with a volatile organic compound, such as TFA [para. 0016]).
It would be obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the biological liquid of modified Kremplova to be selected from blood, plasma, and serum, as taught by Steen, as adding a volatile organic compound, such as TFA, can reduce the noise and background caused by blood constituents (Steen, [para. 0037]).
Regarding Claim 2, modified Kremplova teaches a method for detecting and quantifying a metal element in a biological liquid according to claim 1.
Kremplova teaches separating a protein-containing fraction of the biological liquid from a fraction of the biological liquid comprising the metal element and the TFA (diluted plasma sample with TFA was centrifuged, and then supernatant was used as the sample for electrochemical determination [Section 2.5 Preparation of Samples, page 5900]);
Regarding Claim 7, modified Kremplova teaches the method according to claim 1.
Kremplova is silent on wherein the at least one working electrode is treated with metal nanoparticles and/or a fluorinated polymer.
Cinti teaches wherein the working electrode is treated with metal nanoparticles (ink of screen-printed electrodes can be modified with metal nanoparticles, such as Au or Pt [third para. page 1]).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the working electrode of modified Kremplova to contain metal nanoparticles, as taught by Cinti, as using metal nanoparticles can improve the electroanalytical performance of screen-printed devices (Cinti, [third para. page 1]).
Regarding Claim 8, modified Kremplova teaches the method according to claim 2.
Kremplova teaches wherein the step of separating the protein-containing fraction of the biological liquid from the fraction of the biological liquid comprising the metal element and the at least one fluorinated acid substance is carried out by centrifugation (diluted sample combined with TFA was centrifuged [Section 2.5 Preparation of Samples, page 5900]).
Regarding Claim 10, modified Kremplova teaches the method according to claim 1.
Kremplova teaches wherein the metal element is selected from iron (Fe concentration is based on signal [Section 2.5 Preparation of Samples, page 5900]).
Regarding Claim 11, modified Kremplova teaches the method according to claim 10.
Kremplova teaches wherein the metal element is Fe2+ and Fe3+ (mammalian blood sample [second para. page 5897], which can be in the divalent or trivalent form Fe2+ and/or Fe3+ [first para. page 5895]).
Regarding Claim 15, modified Kremplova teaches the method according to claim 1.
Kremplova teaches wherein an amount of the biological liquid applied to the electroanalytical sensor is 20 µL (volume of injected sample is 20 µL [first para. page 5899]).
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Kremplova, Cinti, and Steen, as applied to claim 1, and in view of Wang et al. (Nafion coated flexible bismuth sensor for trace lead and cadmium determination, Microsystem Technologies, 2018, 24, 3697-3704).
Regarding Claim 6, modified Kremplova teaches the method according to claim 1.
Kremplova is silent on wherein a fluorinated polymer is used in addition to the TFA.
Wang teaches a chemical sensor for sensing metal ions (abstract), and teaches wherein a fluorinated polymer is used (Nafion solution was added to electrode surface [first para. col. 1, page 3699; illustrated in Figure 2, page 3699]).
Modified Kremplova and Wang are considered analogous art to the claimed inventions because they are in the same field of electroanalytic sensors. It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the working electrode of modified Kremplova to include Nafion, which is a fluoropolymer, as taught by Wang, as using Nafion can help to reduce interference caused by surface active compounds and enhance the preconcentration of heavy metal ions, such as lead and cadmium (Wang, [abstract]).
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Kremplova Cinti, and Steen, as applied to claim 2, and in view of Hou et al. (Microfluidic Devices for Blood Fractination, Micromachines, 2011, 2, 319-343).
Regarding Claim 9, modified Kremplova teaches the method according to claim 2.
Kremplova is silent on wherein the step of separating the protein-containing fraction of the biological liquid from the fraction of the biological liquid comprising the metal element and the at least one fluorinated acid substance is carried out by a microfluidic system.
Hou teaches various methods of separating biological fluids using microfluidic devices for blood fractionation (abstract), and teaches separating the protein-containing fraction is carried out by a microfluidic system (for example, blood plasma fractions are separated from diluted blood samples using dielectrophoresis in Figure 2b [page 324]).
Modified Kremplova and Hou are considered analogous art to the claimed inventions because they are in the same field of methods to separate biological liquids. It would be obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the separation step of the protein-containing fraction of modified Kremplova by using a microfluidic device using, for example, dielectrophoretic separation, as taught by Hou, as microfluidic devices offer an alternative method to separating biological fluids, such as whole blood or blood components (Hou, [abstract]). In addition, as Kremplova teaches that TFA is added to the processed plasma sample, centrifuged, with the resulting supernatant used for electrochemical determination, it would be obvious to one of ordinary skill in the art prior to the effective filing date to separate the protein-containing fraction of the biological liquid from the fraction of the biological liquid comprising the metal element and the at least one fluorinated acid substance is carried out by a microfluidic system, as taught by combined Kremplova and Hou, as the microfluidic systems outlined in Hou can be designed to remove the liquid supernatant from the cell debris (example microfluidic system illustrated in Figure 2B of Hou, page 324). The combination of familiar elements is likely to be obvious when it does no more than yield predictable results. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143(I)(A)).
Response to Arguments
Applicant's arguments, see Remarks pgs. 4-8, filed 02/24/2026, with respect to the 35 U.S.C 103 rejections and amended claims have been fully considered.
Applicant’s Argument #1:
Applicant argues on page 6 that for, the 103 rejection, primary reference Kremplova teaches the use of only erythrocytes, as opposed to plasma. As such, Kremplova does not teach “a biological liquid selected from the group consisting of blood, plasma, and serum”. In addition, Kremplova uses several reagents, not just TFA, for sample preparation, which is much more complex compared to the instant application.
Examiner’s Response #1:
Applicant’s arguments have been fully considered, but are moot in view of the new grounds of rejection above. Regarding the use of other reagents, as claim 1 recites the use of “comprising” instead of other verbiage including “consisting of”, as long the sample contacts TFA, additional steps may be used while still reading on the claim 1 instant application. The Examiner recommends changing the verbiage of claim 1 to recite “consisting of” instead of “comprising” if Applicant wishes to highlight the more simplistic method of the instant application to distinguish the instant application over the prior art of record.
Applicant’s Argument #2:
Applicant argues on pages 6-7 that secondary reference Cinti, which is used to teach screen-printed electrodes, is not analogous as Kremplova uses a HMDE working electrode, an Ag/AgCl reference electrode, and a platinum auxiliary electrode. As HMDE is a specialized electrode to detect trace metal, this is fundamentally different from the claimed screen-printed electrodes on cellulose/paper, so one of ordinary skill would not combine Cinti with Kremplova. In addition, cost saving by using a cellulose support does not provide a sufficient rationale for combining these references.
Examiner’s Response #2:
Applicant’s arguments have been fully considered, but are not persuasive. Using cellulose for a cost-saving measure is a valid rationale, as using cellulose is a suitable substrate for detecting metal ions, as Kremplova and Cinti are both analogous references that use electrodes to detect metal ions. In addition, Cinti teaches a cellulose-based substrate for the electrodes of an electroanalytical sensor capable of detecting metal ions (see claim 1 rejection above).
Applicant’s Argument #3:
Applicant argues on pages 7 that, for claim 6, although Wang discloses the use of a Nafion film, bismuth is critical to the working electrode of Wang. Thus, a person of ordinary skill in the art would not have a reasonable expectation of success of just coating the working electrode of Kremplova and Cinti with Nafion.
Examiner’s Response #3:
Applicant’s arguments have been fully considered, but are not persuasive. Although Applicant asserts that bismuth is necessary for the working electrode of Wang, one of ordinary skill could reasonably add Nafion to cover the working electrode, as taught by Wang, to arrive at the instant applications claim 6, which requires a fluorinated polymer. Note that the working electrode is not modified and only a Nafion layer is added to cover the working electrode, and Wang teaches that Nafion can be used to decrease interference (Wang, [abstract and first para. col. 1, page 3698]).
Conclusion
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/R.L.G./Examiner, Art Unit 1795
/LUAN V VAN/Supervisory Patent Examiner, Art Unit 1795