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 .
Status of the Claims
The Amendment filed January 21, 2026 has been entered. Claims 1, 4, 7, 10-11, 13, and 18 have been amended; claims 43-48 are new; and claims 5, 9, 12, 17 and 19-42 have been cancelled. Claims 1-4, 6-8, 10-11, 13-16, 18, and 43-48 are currently pending and examined herein.
Status of the Rejection
Applicant’s amendments to the Claims have overcome each objection previously set forth in the Non-Final Office Action mailed October 22, 2025.
All 35 U.S.C. §103 rejections from the previous office action are essentially maintained and modified only in response to the amendment.
New grounds of rejection under 35 U.S.C. § 103 for new claims 43-48 are necessitated by the amendments as outlined below.
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 1-4, 6-8, 10-11, 13-16, 18, and 43-48 are rejected under 35 U.S.C. 103 as being unpatentable over Marczak et al. (US20180346975A1), and in view of Zenhausern et al. (US20160187293A1) and Marshall et al. (US20190039069A1).
Regarding claim 1, Marczak teaches a method for transfer of a charged substance from a sample to an electrophoresis matrix (A method for separating biomolecules, the method comprising: loading a sample containing a plurality of biomolecules, a plurality of first probes and a plurality of second probes into the electrophoresis matrix; applying a first electric field that causes the plurality of biomolecules, the plurality of first probes and the plurality of second probes to move through the electrophoresis matrix [claim 1; Fig.7E; para. 0065-0067, 0085-0096]), the method comprising:
contacting the sample including the charged substance with the electrophoresis matrix in the presence of an electrolyte (loading a sample containing a plurality of biomolecules, a plurality of first probes and a plurality of second probes into the electrophoresis matrix [claim 1]; A buffer may provide ions to maintain a relatively constant pH value and carry the electrical current through the electrophoresis matrix in the microchannel [para. 0058]);
applying an electric field across the electrophoresis matrix to effect transfer of the charged substance to the electrophoresis matrix (applying an electric field that causes the plurality of biomolecules, the plurality of first probes and the plurality of second probes to move through the electrophoresis matrix [claim 1; Fig.7E; para. 0065-0067, 0085-0096]).
Marczak further teaches the sample may be loaded within or on top of the electrophoresis matrix [para. 0067].
Marczak is silent to: (1) wherein the sample is on a sample collector; (2) contacting the sample collector containing the sample with the electrophoresis matrix; and (3) transferring the charged substance from the sample collector to the electrophoresis matrix under the applied electric field.
Zenhausern teaches an electrophoresis of a sample (abstract and [para. 0149-0154]), wherein the sample may be received from one or more of: a swab, a buccal swab, a cotton swab, a soft swab, a solution, a suspension, an item of clothing, an item placed in the mouth, a cigarette or piece thereof, chewing gum or saliva [para. 0389].
Marshall teaches systems and devices used for processing samples and extracting nucleic acids, for example by isotachophoresis (abstract), wherein the samples include solid tissue, …, buccal swabs, dried blood spots and, or any combination thereof [para. 0009, 0175].
Given the teachings of Marczak regarding the sample may be applied on top surface of the electrophoresis matrix wherein the matrix absorbs the sample [para. 0067]; the teachings of Zenhausern regarding electrophoresis of a sample received from a swab; and the teachings of Marshall regarding isotachophoresis of a sample received from buccal swabs, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the sample in Marczak with a sample on a sample collector of a swab, wherein the sample collector containing the sample including the charged substance is applied on top surface of the electrophoresis matrix, which absorbs the sample, as taught by combined Marczak, Zenhausern, and Marshall, since both Zenhausern and Marshall teach suitable alternative form of the sample on a sample collector for electrophoretic separation ([para. 0389 in Zenhausern] and [para. 0175 in Marshall]).
With the above substitution, modified Marczak teaches the sample on the sample collector of a swab; contacting the sample collector containing the sample including the charged substance with the electrophoresis matrix in the presence of an electrolyte (the sample collector is applied on the top surface of the electrophoresis matrix, where adsorbs the sample); and applying the electric field across the electrophoresis matrix to effect transfer of the charged substance from the sample collector to the electrophoresis matrix.
Regarding claim 2, modified Marczak teaches the method of claim 1, and Marczak teaches wherein the electrophoretic matrix comprises a thread (a microchannel having a first end and a second end and containing an electrophoresis matrix. In some embodiments, the electrophoresis matrix may comprise at least one of a gel, paper, fabric or thread [para. 0049]. A thread electrophoresis matrix may contain one or more threads aligned parallel to each other along the microchannel. Threads can be derived from natural materials, such as cotton and silk, or can be made using synthetic biomaterials [para. 0057]).
Regarding claim 3, modified Marczak teaches the method of claim 1, wherein the sample collector is a swab (as outlined in the rejection of claim 1 above, the sample collector is a swab).
Regarding claim 4, modified Marczak teaches the method of claim 1, and Marczak does not explicitly teach wherein at least 50% of the charged substance is transferred from the sample collector to the electrophoresis matrix on the application of the electric field.
However, Marczak teaches wherein Fig.2A shows nanoparticle/DNA mixture is inserted into sample inlet, and Fig.2B shows sample packs tightly against the membrane during the enrichment step after application of an electric field [para. 0009]. Since the sample loading region is completely clear, and sample packs tightly against the membrane (see Fig.2B), nearly 100% charged substance is transferred from the sample loading region where the sample collector is positioned to the electrophoresis matrix on the application of an electric field since the electrophoresis matrix adsorbs the sample and then charged substance electrophoretically migrates to the membrane under the applied electric field due to the generated electrophoretic force. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that nearly 100% of the charged substance is transferred from the sample collector to the electrophoresis matrix on the application of an electric field due to the adsorption of the electrophoresis matrix and electrophoretic migration of the charged substance under the applied electric field.
Regarding claim 6, modified Marczak teaches the method of claim 1, and Marczak teaches further comprising moving the charged substance along the electrophoresis matrix through electrophoresis or isotachophoresis away from the location of initial transfer of the charged substance onto the electrophoresis matrix (applying a first electric field that causes the plurality of biomolecules, the plurality of first probes and the plurality of second probes to move through the electrophoresis matrix towards the ion permselective membrane whereupon the plurality of biomolecules, the plurality of first probes and the plurality of second probes become concentrated in the electrophoresis matrix adjacent to the ion permselective membrane [para. 0045]. Fig.1c shows the positions of the “membrane” and “sample loading”).
Regarding claim 7, modified Marczak teaches the method of claim 6, and Marczak teaches wherein the charged substance is moved along the electrophoresis matrix to an operation reservoir (see Fig.1 and 7E; applying a first electric field that causes the plurality of biomolecules, the plurality of first probes and the plurality of second probes to move through the electrophoresis matrix towards the ion permselective membrane [para. 0045]; thus, the charged substance is moved along the electrophoresis matrix to the membrane reservoir), in which an operation is performed on the charged substance (applying a second electric field to form an ion depletion front as a result of ion concentration polarization, whereupon the ion depletion front moves away from the ion permselective membrane. As the ion depletion front moves away from the ion permselective membrane, linked nanoparticle multimers at the ion depletion front precipitate aggregate and precipitate. Further comprising quantifying the precipitated linked nanoparticle multimers [para.0092-0098]; The aggregated particles are repacked against the membrane for detection [para. 0009; Fig.2D]).
Regarding claim 8, modified Marczak teaches the method of claim 1, and Marczak teaches further comprising performing an operation on the charged substance after its transfer to the electrophoresis matrix, the operation selected from the group consisting of detection (applying a first electric field that causes the plurality of biomolecules, the plurality of first probes and the plurality of second probes to move through the electrophoresis matrix towards the ion permselective membrane whereupon the plurality of biomolecules, the plurality of first probes and the plurality of second probes become concentrated in the electrophoresis matrix adjacent to the ion permselective membrane [para. 0045]. applying a second electric field to form an ion depletion front as a result of ion concentration polarization, whereupon the ion depletion front moves away from the ion permselective membrane and whereupon linked nanoparticle multimers at the ion depletion front aggregate and precipitate and whereupon biomolecules, first probes and second probes not contained within a linked nanoparticle multimer move through the electrophoresis matrix away from the ion permselective membrane behind the ion depletion front [para. 0093]. The linked nanoparticle multimers may be quantified for measuring the intensity of light absorption or emission of the nanoparticles. Once a measurement of the intensity of the light absorption or emission is known, a comparison to a standard curve may provide quantification of the sample [para. 0098]; The aggregated particles are repacked against the membrane for detection [para. 0009; Fig.2D]).
Regarding claim 10, modified Marczak teaches the method of claim 6, and Marczak teaches further comprising: subjecting the charged substance transferred onto the electrophoresis matrix to electrophoresis to separate a target analyte that forms a component of the charged substance into a focused band on the electrophoresis matrix (see Figs.1B, 2C-2D, and 6A-6F [para. 0008-0009, 0123]; SEM images of the two different bands were collected. To carry out the collection, a special chip was used where clear packaging tape replaced the bottom surface. After the depletion step separated the nanoparticles, the tape was peeled off, the two bands were cut from the gel, and then they were placed into separate containers in 20 mL of water [para. 0117]).
Regarding claim 11, modified Marczak teaches the method of claim 10, and Marczak teaches further comprising detecting the presence of the target analyte, wherein the detecting step comprises detecting the target analyte as the focused band of the target analyte on the electrophoresis matrix passes through a detection zone of the electrophoretic matrix (The aggregated particles are repacked against the membrane for detection [para. 0009; Fig.2D]; a fluorescein doped gel to track the movement of the depletion region and simultaneously monitored the aggregation and separation of the nanoparticles [para. 0123; Figs. 6A-6D]; Fluorescence or visible absorption images can be quantified using standard pixel intensity software, such as ImageJ. Once a measurement of the intensity of the light absorption or emission is known, a comparison to a standard curve may provide quantification of the sample [para. 0098]).
Regarding claim 13, modified Marczak teaches the method of claim 1, wherein the electrophoresis matrix is open to an environment to enable modifications to be made on the electrophoresis matrix (the sample maybe loaded on top of the electrophoresis matrix [para. 0067 in Marczak]; as outlined in the rejection of claim 1 above, the sample collector of a swab containing the sample is applied/loaded on top surface of the electrophoresis matrix wherein the matrix absorbs the sample. Thus, the electrophoresis matrix is open for loading/applying the sample collector on top surface of the electrophoresis matrix to enable modifications to be made on the electrophoresis matrix [sample is adsorbed by the matrix]).
Regarding claim 14, modified Marczak teaches the method of claim 13, and Marczak teaches wherein the electrophoresis matrix is in the form of a thread (the electrophoresis matrix may comprise at least one of a gel, paper, fabric or thread. A thread electrophoresis matrix may contain one or more threads aligned parallel to each other along the microchannel. Threads can be derived from natural materials, such as cotton and silk, or can be made using synthetic biomaterials [para. 0049, 0057]).
Marczak further teaches the electrophoresis matrix is cut to isolate a portion of the electrophoresis matrix containing the charged substance (To carry out the collection, a special chip was used where clear packaging tape replaced the bottom surface. After the depletion step separated the nanoparticles, the tape was peeled off, the two bands were cut from the gel, and then they were placed into separate containers in 20 mL of water [para. 0117]).
Marczak does not explicitly teach the thread is cut to isolate a portion of the thread containing the charged substance.
Given the teachings of Marczak regarding the electrophoresis matrix can be in the form of a gel or thread, and the electrophoresis matrix of gel is cut to isolate a portion of the electrophoresis matrix containing the charged substance, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use a thread as the electrophoresis matrix and the thread is cut to isolate a portion of the thread containing the charged substance, since thread is a suitable alternative to the gel as the electrophoresis matrix [para. 0049, 0057 in Marczak].
Regarding claim 15, modified Marczak teaches the method of claim 14, and Marczak teach further comprising recovery of the charged substance from the cut portion of the electrophoresis matrix (After the depletion step separated the nanoparticles, the tape was peeled off, the two bands were cut from the gel, and then they were placed into separate containers in 20 mL of water. The solutions were heated at 60° C. for twenty minutes to melt the gel. The solutions were then dispensed onto silicon substrates and evaporated. Following evaporation, the substrates were washed with water to remove any residual salt. The dried particles were imaged by a Carl Zeiss EVO-50 SEM. The subsequent images were analyzed in ImageJ using the “Analyze Particles” function to determine the area of the particles from which the diameter was then calculated [para. 0117]).
As outlined in the rejection of claim 14 above, the thread is used as the electrophoresis matrix and the two bands were cut from the thread. Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the recovery of the charged substance from the cut portion of the gel to recovery of the charged substance from the cut portion of the thread since thread is a suitable alternative to the gel as the electrophoresis matrix [para. 0049, 0057 in Marczak].
Regarding claim 16, modified Marczak teaches the method of claim 1, and Marczak teaches wherein the electric field is applied across the electrophoresis matrix via a pair of electrodes positioned to apply the electric field along the electrophoresis matrix (a first electrode and a second electrode configured to apply an electric field. The electrodes may be in direct contact with the electrophoresis matrix or in a buffer reservoir located at either end of the electrophoresis matrix or adjacent to the ion permselective membrane [para. 0064]; Fig.7E), wherein a first electrode of the pair of electrodes is positioned in a first electrolyte reservoir, and the second electrode of the pair of electrodes is positioned in a second electrolyte reservoir (Fig.7E shows a first electrode positioned in a membrane reservoir and a second electrode positioned in gel inlet reservoir), and wherein the electrophoresis matrix extends between the first and second electrolyte reservoirs and is in electrical connection with the first and second electrodes (see Fig.7E).
Regarding claim 18, modified Marczak teaches the method of claim 16, and Marczak teaches comprising transfer of the charged substance from the sample collector to the electrophoresis matrix (i) in said first electrolyte reservoir (membrane reservoir as shown in Figs. 1A and 7E; applying a first electric field that causes the plurality of biomolecules, the plurality of first probes and the plurality of second probes to move through the electrophoresis matrix towards the ion permselective membrane [para. 0086]; Sample packs tightly against the membrane during the enrichment step [para. 0009; Fig.2B]).
Regarding claim 43, modified Marczak teaches the method of claim 4, wherein at least 70% of the charged substance is transferred from the sample collector to the electrophoresis matrix on the application of the electric field (as outlined in the rejection of claim 4 above, modified Marczak teaches nearly 100% charged substance is transferred from the sample loading region where the sample collector is positioned to the electrophoresis matrix on the application of an electric field. Furthermore, the claimed limitation is an intended result of a positively recited step. The court noted that a "‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’" Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003))).
Regarding claim 44, modified Marczak teaches the method of claim 43, wherein at least 90% of the charged substance is transferred from the sample collector to the electrophoresis matrix on the application of the electric field (as outlined in the rejection of claim 43 above, modified Marczak teaches nearly 100% charged substance is transferred from the sample loading region where the sample collector is positioned to the electrophoresis matrix on the application of an electric field. Furthermore, the claimed limitation is an intended result of a positively recited step. The court noted that a "‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’" Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003))).
Regarding claim 45, modified Marczak teaches the method of claim 7, and Marczak teaches wherein the operation is detection (applying a second electric field to form an ion depletion front as a result of ion concentration polarization, whereupon the ion depletion front moves away from the ion permselective membrane. As the ion depletion front moves away from the ion permselective membrane, linked nanoparticle multimers at the ion depletion front precipitate aggregate and precipitate. Further comprising quantifying the precipitated linked nanoparticle multimers [para.0092-0098]; The aggregated particles are repacked against the membrane for detection [para. 0009; Fig.2D]).
Regarding claim 46, modified Marczak teaches the method of claim 18, and Marczak teaches further comprising moving the charged substance along the electrophoresis matrix from the first electrolyte reservoir to an operation reservoir for performance of an operation on the charged substance (applying a second electric field to form an ion depletion front as a result of ion concentration polarization, whereupon the ion depletion front moves away from the ion permselective membrane. As the ion depletion front moves away from the ion permselective membrane, linked nanoparticle multimers at the ion depletion front precipitate aggregate and precipitate. Further comprising quantifying the precipitated linked nanoparticle multimers [para.0092-0098]; Sample is loaded into cross-channel [Fig.7A]. Enrichment drives particles towards membrane [Fig.7B]. Depletion separates monomers from aggregate possessing target [Fig.7C]. Particles are repacked at membrane for quantification [Fig.7D]; Profile view of one channel [Fig. 7E]. The three remaining channels intersect at the membrane and have identical electrode placement [para. 0014]; A 6.9 mm diameter hole was placed in the center of the chip to hold the membrane cast. A 4 mm×4 mm cation-exchange membrane was sealed to the bottom of the cast and remained flush with the top of the microfluidic channel [para. 0107]. The hole holding the cation-exchange membrane disposed at the center of the chip is deemed as the operation reservoir ).
Regarding claim 47, modified Marczak teaches the method of claim 16, and Marczak teaches wherein the electrophoretic matrix is in the form of a thread (a microchannel having a first end and a second end and containing an electrophoresis matrix. In some embodiments, the electrophoresis matrix may comprise at least one of a gel, paper, fabric or thread [para. 0049]. A thread electrophoresis matrix may contain one or more threads aligned parallel to each other along the microchannel. Threads can be derived from natural materials, such as cotton and silk, or can be made using synthetic biomaterials [para. 0057]. Thus, the electrophoretic matrix is in the form of a thread).
Regarding claim 48, modified Marczak teaches the method of claim 16, and Marczak teaches wherein the sample is a biological sample (a sample containing a plurality of biomolecules, a plurality of first probes and a plurality of second probes [para. 0045]), but is silent to wherein the biological sample is selected from the group consisting of saliva, blood, cells, cell lining and mucous.
Zenhausern does teach wherein the sample may be received from saliva [para. 0389]. The sample may be saliva sample [para. 0390].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the sample of modified Marczak to a saliva sample, as taught by Zenhausern, since Zenhausern teaches saliva sample as a suitable alternative sample for the analysis [para. 0389-0390].
Response to Arguments
Applicant's arguments, see Remarks Pgs. 5-9, filed 1/21/2026, with respect to the 35 U.S.C. § 103 rejections have been fully considered, but are not persuasive.
Applicant’s Argument #1:
Regarding claims 1-4, 6-8, 10-11, 13-16, and 18, applicant argues at pages 5-8 that "applying an electric field across the electrophoresis matrix to effect transfer of the charged substance from the sample collector to the electrophoresis matrix" is that the charged substance can be directly transferred from the sample collector to the electrophoresis matrix without an intervening transfer or diffusion into a bulk electrolyte and out of a bulk electrolyte. This allows for the efficient and quick transfer of the charged substance from the sample collector to the electrophoresis matrix. In Marczak, an electric field is not used or contemplated as a mechanism by which the charged substance may be transferred from a collector into the matrix. Rather, an electric field is used for performing electrophoresis only, and only after a sample has been loaded by other means. In Zenhausern, a sample is introduced into the device by physical means and moved through various chambers and channels by electrochemical pumps, not by electrophoresis or any applied electric field at this stage. In Marshall, a sample is introduced into the device by physical means prior to the application of an electric field for isotachophoresis. Thus, none of the cited references discloses or suggests "applying an electric field across the electrophoresis matrix to effect transfer of the charged substance from the sample collector to the electrophoresis matrix." Dependent claims and new claims are patentable for at least similar reasons for claim 1.
Examiner’s Response #1:
Applicant’s arguments have been fully considered, but are not persuasive. Firstly, in response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., the charged substance can be directly transferred from the sample collector to the electrophoresis matrix without an intervening transfer or diffusion into a bulk electrolyte and out of a bulk electrolyte) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Secondly, as outlined in the rejection of claim 1 above, modified Marczak teaches the sample on the sample collector of a swab; contacting the sample collector containing the sample including the charged substance with the electrophoresis matrix in the presence of an electrolyte (the sample collector is applied on the top surface of the electrophoresis matrix, where adsorbs the sample); and applying the electric field across the electrophoresis matrix to effect transfer of the charged substance from the sample collector to the electrophoresis matrix. Note that the sample collector [swab] is applied on the top surface of the electrophoresis matrix, and Marczak teaches applying an electric field across the electrophoresis matrix to effect transfer of the charged substance to the electrophoresis matrix (applying an electric field that causes the plurality of biomolecules, the plurality of first probes and the plurality of second probes to move through the electrophoresis matrix [claim 1; Fig.7E; para. 0065-0067, 0085-0096]).
Thirdly, regarding the arguments that in the prior arts the sample has been introduced into the device by physical means prior to the application of an electric field, the instant claim 1 recites “contacting the sample collector containing a sample including the charged substance with the electrophoresis matrix in the presence of an electrolyte; and applying an electric field across the electrophoresis matrix to effect transfer of the charged substance from the sample collector to the electrophoresis matrix”, thus in instant claim 1 the sample is also introduced into the device in order to contact the electrophoresis matrix prior to the application of the electric field. Instant claim 1 does not recite the means to contact the sample collector containing a sample including the charged substance with the electrophoresis matrix during the contacting step. Note that the feature of the contacting step occurring in the presence of the applied electric field is not recited in the rejected claim 1.
Examiner suggests applicant to amend claim 1 by reciting features upon which applicant relies (i.e., contacting the sample collector with the electrophoresis matrix during the application of an electric field across the electrophoresis matrix).
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SHIZHI QIAN whose telephone number is (571)272-3487. The examiner can normally be reached Monday-Thursday 8:00 am-5:00 pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Luan V Van can be reached on 571-272-8521. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SHIZHI QIAN/Examiner, Art Unit 1795