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 .
Election/Restrictions
Applicant's election with traverse of group I, claims 1, 4, 8, 10, 12-16, 18, 20, 23, 29, 31-32, in the reply filed on 04/14/2026 is acknowledged. The traversal is on the ground(s) that the present application involves a gold nanocluster of five gold atoms and a size of 3-5 nm that has a fluorescent color which can fade at different rates according to cyanide concentration. It is respectfully noted that the presently pending claims requires 15 gold atoms, not five. Further, in the instant specification page 15 line 15 it describes that there are 15 gold atoms.
With respect to Applicant’s traversal of the restriction requirement, Applicant’s arguments are based on the presently amended claims having a technical feature not taught by the references cited in the restriction requirement set forth in the office action mailed 03/13/2026. However, the restriction requirement was properly made with respect to the claims presented at the time of the previous office action (i.e., the claims as originally presented) and Applicant has not presented any arguments directed to the original claims. Also, even with respect to the newly amended claims, the amended claims do not make a contribution over the prior art (i.e., Groups I and II still lack the same or corresponding special technical feature) because the groups do not make a contribution over the prior art, namely Saiki (US-2009/0246082-A1) in view of Shojaeifard et al. “Efficient On-Off Ratiometric Fluorescence Probe for Cyanide Ion Based on Perturbation of the Interaction between Gold Nanoclusters and a Copper(II)-Phthalocyanine Complex” herein Shojaeifard, Combes et al. “Functionalized Au15 nanoclusters as luminescent probes for protein carbonylation detection” herein Combes, and alternatively in view of Yang et al. “Structural and optical properties of pencillamine-protected gold nanocluster fractions separated by sequential size-selective fractionation” herein Yang and Halawa et al. “Gold nanoclusters: synthetic strategies and recent advances in fluorescent sensing” herein Halawa as set forth in the 103 section below.
Applicant argument regarding structural precision and molecular characterization, please note that these arguments are directed to newly added claim amendments not present when the Office Action mailed 03/13/2026 was mailed.
Applicant arguments on purification and stability protocols, where the protocol includes a specific filtration step using 0.2-0.5 µm pore sizes to remove excess BSA. Firstly, this limitation was not present when the Office Action mailed 03/13/2026 was mailed. Second, these limitations are part of group II, and is not a shared technical feature in the presently pending claims.
Applicant arguments on matrix complexity and clinical application where the claimed invention is for whole blood and plasma. It is respectfully noted that the shared technical feature from the Office Action mailed 03/13/2026 was the gold nanoparticle clusters. It was not a requirement that the sample specifically be blood for the restriction.
Applicant arguments on integrated autonomous hardware, these arguments are not directed to the shared technical feature based on the Office Action mailed 03/13/2026.
Applicant arguments on optimized excitation and digital diagnosis, these arguments are not directed to the shared technical feature based on the Office Action mailed 03/13/2026.
Applicant arguments on operational superiority and practical utility, these arguments are not directed to the shared technical feature based on the Office Action mailed 03/13/2026.
The requirement is still deemed proper and is therefore made FINAL.
Claims 33-34, 44, 49-50 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 04/14/2026.
Status of Claims
Claims 1, 4, 8, 10, 12-16, 18, 20, 23, 29, 31-34, 44, 49-50 remain pending in the application, with claims 1, 4, 8, 10, 12-16, 18, 20, 23, 29, 31-32 being examined and claims 33-34, 44, 49-50 being withdrawn pursuant to the election filed 04/14/2026.
Drawings
The drawings are objected to under 37 CFR 1.83(a). The drawings must show every feature of the invention specified in the claims. Therefore, the bottom PMMA layer having holes that allow the blood sample to be filled for cyanide detection and ventilation holes in order to adjust eh required pressure and to prevent the formation of air bubbles during filling as described in claim 23 must be shown or the feature(s) canceled from the claim(s). No new matter should be entered.
While Figure 2 does show the bottom layer, it is difficult to tell if the marks on the bottom layer 25 are the holes and ventilation holes.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because of the following informalities:
Please note that the title appears to have a typo as it recites “cynadide”. Throughout the instant specification it describes detecting detection of cyanide.
Page 1 in the title recites “cynadide” and page 4 line 27 recites “cynadide” where this appears to be a typo because throughout the instant specification it describes detecting cyanide.
Page lines 5-6 recites “The bottom PMMA layer (25) of the compact disc (2) comprises no functional channels or holes and serves as a supporting platform for the other layers.” However, on page 9 lines 26-29 it describes the bottom layer comprises holes that allow the blood sample to be filled and ventilation holes in order to adjust the required pressure and to prevent formation of air bubbles during filling.
These two sections of the specification appear contradict each other, where one says the bottom layer does not have any functional channels or holes, but then later states that it does.
Appropriate correction is required.
Claim Objections
Claims 1, 4, 8, 10, 12-16, 18, 20, 23, 29, 31-32 are objected to because of the following informalities:
Claims 4, 8, 10, 12-16, 18, 20, 23, 29, 31-32 all recite “A system (1)” in the preamble which should be amended to be “[[A]] The system (1)” to make it clear that all dependent claims are referring to the system of claim 1.
Claim 1 lines 7-8 recites “at least one chamber having an area wherein the plasma of a blood sample, which is a biological sample, can be filled to be separated;” where this phrasing is somewhat unclear because it sounds like plasma is being added to the chamber and is then separated. However, lines 10-11 then describes plasma of a blood sample being separated.
It is suggested to have lines 7-8 recite “at least one chamber having an area wherein
Please note 112b section below where the inconsistency with referring to the sample is discussed, which could potentially affect how the suggestion for lines 7-8 is written.
Lines 17-18 recites “at least one electronic device (5) which is configured to enable to capture image for the purpose of determination” on lines 17-18, and “corresponding to the colors in the images captured” on lines 22-23 where it is somewhat unclear because lines 17-18 makes it sound like a single image is captured, but then lines 22-23 it recites multiple images. Lines 17-18 are additionally phrased awkwardly.
It is suggested to amend lines 17-18 to recite “configured to capture images for the purpose of determination”
Claim 13 recites “which comprises the middle PMMA layer (23) with the middle PMMA layer (23) configured to be the place” where this phrasing reads awkwardly, as it almost sounds as though there is another middle PMMA layer.
It is suggested to amend claim 13 to recite “which comprises the middle PMMA layer (23), whereinis configured to be the place” or similar.
Claim 20 recites “the composition of plasma and AuNC in the plasma” where it is suggested that “composition” be “combination” instead, as claim 1 describes a combination of gold nanoclusters and the cyanide-containing plasma.
Appropriate correction is required.
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 1, 4, 8, 10, 12-16, 18, 20, 23, 29, 31-32 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 1
Line 2 recites “the living beings” where there is insufficient antecedent basis for this limitation, as no living beings have been recited prior.
Line 3 recites “the industry and/or house fires” where there is insufficient antecedent basis for this limitation, as no industry and/or house fires has been recited prior.
Line 7 recites “wherein the plasma of a blood sample, which is a biological sample, can be filled to be separated” where first there is insufficient antecedent basis for “the plasma” as no plasma has been recited prior. Second, it is unclear if “a biological sample” is meant to be the same or different from biological samples recited on line 2. Third, the way line 7 is phrased is somewhat unclear as it sounds that plasma is added and is then separated. However, further description in lines 10-11 describes separating the blood sample into its plasma. In other words, on line 7 is plasma being further separated, or is the blood sample being separated into plasma?
For examination, it will be interpreted that the biological sample on line 7 is the same as the one described on line 2, and that further the blood sample is separated into plasma.
Line 10 recites “the centrifugation process” where there is insufficient antecedent basis for this limitation, as no centrifugation process has been recited prior.
Line 11 recites “in the compact disc (2) into its plasma” where it is unclear if the plasma of line 11 is the same or different from the plasma described on line 7.
For examination it will be interpreted that it is the same plasma.
Lines 15-16 recites “the cyanide concentration” where there is insufficient antecedent basis for this limitation. While lines 1-4 do describe cyanide determination, a cyanide concentration has not been previously positively recited and therefore it is unclear what cyanide concentration is being referred to.
Lines 18-19 recites “of fluorescent colors of the combination of gold nanoclusters (4) and the cyanide-containing plasma” where it is unclear if the gold nanoclusters are the same or different from the ones described previously. Further, only a gold nanocluster has been described prior and it is unclear how there is now multiple of them.
Lines 19-20 recites “the amount of cyanide” where there is insufficient antecedent basis for this limitation. While lines 14-15 does describe cyanide concentration, it is understood that concentration and amount are different things. Please note that line 22 also recites “the amounts of cyanide”
Throughout claim 1, it is suggested to keep the phrasing of the blood sample consistent. Either call the sample the same thing throughout, or describe what happens to the sample but then refer to the sample as that moving forward. For example, describing that the device receives a blood sample, where then the centrifuge separates the blood from its plasma, then the gold nanocluster interacting with cyanide in the plasma.
Claims 4, 8, 10, 12-16, 18, 20, 23, 29, 31-32 are rejected by virtue of being dependent on a rejected claim.
Claim 4 recites “the compact disc (2) which comprises three polymethylmethacrylate (PMMA) layers” on line 1 where it is unclear if these PMMA layers are the same or different from the at least one layer described in claim 1.
For examination, it will be interpreted that the PMMA layers are the same as the at least one layer.
It is suggested to amend line 1 to recite “the compact disc (2) which comprises the at least one layer, wherein the at least one layer comprises three polymethylmethacrylate (PMMA) layers” or similar.
Lines 2-3 recites “the top (21), the middle (23), and the bottom (25)” and “the first adhesive (22) and the second adhesive (24)” on line 4, where there is insufficient antecedent basis for these limitations.
It is suggested to amend claim 4 to recite “– namely a top (21), a middle (23) and a bottom (25) one – and double-sided tape layers with adhesive properties – namely, a first adhesive (22) anda second adhesive (24) – to be placed between these layers (21, 23, 25).”
Claims 8, 10, 12-16, 18, 20, 23 are rejected by virtue of being dependent on a rejected claim.
Claim 8 recites “the filing (231), the separation (232), the pneumatic (233), the plasma collection (234) and the comparison chamber (235).” on lines 3-4 where there is insufficient antecedent basis for these different chambers.
Additionally, it is unclear if these chambers are in addition to the at least one chamber described in claim 1.
For examination, it will be interpreted that the five chambers are the same as the at least one chamber described in claim 1.
It is suggested to amend claim 8 to recite “the middle PMMA layer (23) , wherein the at least one chamber comprises a filing (231), a separation (232), a pneumatic (233), a plasma collection (234) and a comparison chamber (235).”
Claims 10, 12-16, 18, 20, 23 are rejected by virtue of being dependent on a rejected claim.
Claim 10 recites “the channel from the separation chamber (232) to the pneumatic chamber (233)” on line 3 where it is unclear if the channel being described is the same or different from the second channel from line 2.
Additionally, it is unclear if the channel and the second channel is in addition to the at least one channel described in claim 1. For examination it will be interpreted that the channel and the second channel of claim 10 is the at least one channel described in claim 1.
From the way that claim 10 is phrased, it appears that “the channel” is different from “the second channel” where it is first describing plasma passing through “the channel” from the separation chamber to the pneumatic chamber, and then plasma passes from the pneumatic chamber to the plasma collection chamber via “the second channel”. Looking at the instant specification Figure 4, this appears to be the case.
Therefore, for examination it will be interpreted that the second channel and “the channel” are different from one another.
Lines 4-5 recites “the separation process” where there is insufficient antecedent basis for this limitation, as no separation process has been described prior.
Claim 12 recites “the cyanide content.” on line 4, where there is insufficient antecedent basis for this limitation. While claim 1 does describe a cyanide concentration and an amount of cyanide, it is unclear if cyanide content would be the same measurement.
It is suggested to keep what is being measured consistent.
Claim 14 recites “with pneumatic chamber (233)” where it is unclear if this pneumatic chamber is the same or different from the one described prior.
For examination it will be interpreted that they are the same, and claim 14 should be amended to recite “with the pneumatic chamber (233)”
Claim 15 recites “the plasmas” on line 3 where it is unclear how there is now multiple plasma. Are there multiple samples?
Line 4 recites “blood by AuNCs” where it is unclear if the AuNCs are the same or different from the AuNCs described in claim 1.
For examination, it will be interpreted that they are the same and thus line 4 should be recited to “blood by the AuNCs”
Further, the way claim 15 is phrased is somewhat unclear. It recites “wherein the plasmas that are collected in the pneumatic chamber (233) by being separated from the blood by AuNCs are mixed with each other.” where it almost sounds like the plasmas are separated from blood by an action of the AuNCs, but are then mixed together.
The instant specification on page 8 lines 27-31 and page 9 lines 1-5 describes where the plasma collection chamber contains AuNC solution and empty volume for the plasma leaving the blood to come in.
Therefore, for examination it will be interpreted that claim 15 is describing that the plasma collection chamber receives the plasma and mixes the plasma with AuNCs.
Claim 16 recites “the AuNC solution” on line 3 where there is insufficient antecedent basis for this limitation, as no AuNC solution has been recited prior.
For examination, it will be interpreted that the AuNC solution is referring to the AuNC of claim 1.
Claim 20 recites “the fluorescent color emitted by AuNCs that do not comprise plasma.” on lines 4-5, where it is unclear if the AuNCs and plasma are the same or different from the ones described previously.
For examination, it will be interpreted that the AuNCs are the same, and that the plasma is the same where the comparison chamber does not have the plasma that has been separated out previously.
Claim 29 recites “of cyanide-containing samples” on line 2 where it is unclear if these cyanide-containing samples are the same or different from the cyanide-containing blood sample recited previously.
For examination it will be interpreted that they are the same.
Line 4 recites “with AuNCs” where it is unclear if these are the same or different from the ones recited prior.
For examination it will be interpreted that they are the same.
Claim 31 recites “the color data in the image”, where there is insufficient antecedent basis for the color data as no color data has been recited prior, and it is unclear if this image is the same or different from the images recited in claim 1. Where if it is the same image, since claim 1 recites “images” it is unclear if claim 31 is now calling out a specific image.
Line 4 recites “the database” where there is insufficient antecedent basis for this limitation, as no database has been recited prior.
Line 5 recites “the cyanide reference values” where there is insufficient antecedent basis for this limitation, as no cyanide reference values has been recited prior.
Claim 32 is rejected by virtue of being dependent on a rejected claim.
Claim 32 contains the trademark/trade name Color Grab. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe an application to present values through the L*a*b* color system for color changes and, accordingly, the identification/description is indefinite.
Additionally, “the Color Grab application” has insufficient antecedent basis because no Color Grab application has been recited prior.
Further, line 3 recites “fading mechanisms of AuNCs.” where it is unclear if these AuNCs are the same or different from the ones recited prior.
For examination it will be interpreted that they are the same.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1, 29, 31 is/are rejected under 35 U.S.C. 103 as being unpatentable over Saiki (US-2009/0246082-A1) in view of Shojaeifard et al. “Efficient On-Off Ratiometric Fluorescence Probe for Cyanide Ion Based on Perturbation of the Interaction between Gold Nanoclusters and a Copper(II)-Phthalocyanine Complex” herein Shojaeifard, Combes et al. “Functionalized Au15 nanoclusters as luminescent probes for protein carbonylation detection” herein Combes, and alternatively in view of Yang et al. “Structural and optical properties of pencillamine-protected gold nanocluster fractions separated by sequential size-selective fractionation” herein Yang and Halawa et al. “Gold nanoclusters: synthetic strategies and recent advances in fluorescent sensing” herein Halawa.
Regarding claim 1, Saiki teaches a system (analysis apparatus 1000) ([0064], Figure 2); characterized in that it comprises:
-at least one microfluidic compact disc (CD) (analysis device 101) configured for use with microliter sized samples which consists of at least one layer (substrates 1 and 2) having at least one channel and at least one chamber having an area wherein the plasma of a blood sample, which is a biological sample, can be filled to be separated ([0056], Figures 1, 19, in particular Figure 19 which has a plurality of chambers and channels, [0204] describing embodiment 6 which is seen in Figures 19-22 that describes blood can be separated into blood plasma and blood cells);
- at least one centrifuge device (motor 102) whereon the compact disc (101) is placed and which enables the centrifugation process that is required to separate the blood sample in the compact disc (101) into its plasma ([0064] see analysis device 101 mounted on motor 102 which is a rotation drive means, Figure 2);
The limitations “A portable system which enables to carry out cyanide determination in biological samples taken from the living beings who are exposed to cyanide gas and/or cyanide components released from the industry and/or house fires”, “at least one microfluidic compact disc (CD) (2) configured for use with microliter sized samples”, and “at least one portable centrifuge device (3) whereon the compact disc (2) is placed and which enables the centrifugation process” are directed to the function of the apparatus and/or the manner of operating the apparatus, all the structural limitations of the claim has been disclosed by Saiki and the apparatus of Saiki is capable of being portable, carrying out cyanide determination, being used with microliter sized samples, and enabling a centrifugation process. As such, it is deemed that the claimed apparatus is not differentiated from the apparatus of Saiki (see MPEP §2114).
Please note that the biological sample, which contains cyanide, has not been positively recited in the claim, and is therefore not a part of the claimed system.
While Saiki does describe a measurement cell 37 seen in Figure 19 that mixes/reacts a solution component with a reagent to measure the absorbance or turbidity of the mixed solution (Saiki; [0195]), Saiki does not specify what reagent is used.
Additionally, while Saiki does teach where there is a control circuit 108, A/D converter 109, transmitted light amount signal processing circuit 110, memory 113, CPC 111, and display unit 112 which are understood to be components of at least one electronic device, Saiki teaches the use of a photodetector 107 for detecting the amount of light transmitted through the analysis device 107 (Saiki; [0066]), where a photodetector is understood to not be taking images.
Therefore, Saiki does not teach:
- a gold nanocluster (AuNC) (4) consisting of 15 gold atoms and having a size of 3 -5 nm which is located in the compact disc (2), has a fluorescent color emitting property, and the fluorescent color of which can fade at different rates according to the cyanide concentration by interacting with the cyanide in the plasma when it is combined with the plasma separated from the cyanide-containing blood sample;
- at least one electronic device (5) which is configured to enable to capture image for the purpose of determination of fluorescent colors of the combination of gold nanoclusters (4) and the cyanide-containing plasma under UV light in order to determine the amount of cyanide in the blood plasma under examination; and
- at least one application (6) which is executed on the electronic device (5) and configured to determine the amounts of cyanide corresponding to the colors in the images captured by the electronic device (5).
In the same problem solving area of selective and sensitive determination of an analyte in a biological sample, Shojaeifard teaches a ratiofluorescent sensor for the sensitive and selective detection of cyanide ions in aqueous media (Shojaeifard; abstract).
Specifically, Shojaeifard teaches AuNCs/Cu(PcTs) probes that can detect cyanide anion in blood serum as a biological sample (Shojaeifard; abstract). Shojaeifard teaches gold nanoclusters with glutathione (GSH) ligand caps (Shojaeifard; page 15178 column 1 paragraph 4). It is further described on page 15181 column 1 paragraph 2 in reference to Scheme 1 and Figure 3 that addition of CN- ion causes a decrease in the fluorescence intensity of the nanoclusters. Additionally as seen in Figure 7 on page 15183 the plot shows the change in the color of the ratiometric probe as a function of CN- concentrations. Shojaeifard teaches where gold nanoclusters have sizes smaller than 3 nm (Shojaeifard; page 15178 column 1 paragraph 3).
Shojaeifard further teaches on page 15182 column 2 in section 3.4.1 Colorimetric Determination section that the color change observed by the naked eye was considered as a feasible and simple way to indicate the presence of an analyte, where changes in the intensities in the red and blue emission wavelengths the fluorescence color of the AuNCs/Cu(PcTs) solution was changed by adding CN- anion. Further described in this section, it describes the distinguishable color change by the naked eye under UV lamp and that images are recorded by a smart mobile phone were analyzed and the color value plotted against concentration of CN- to obtain an image analysis based calibration curve, where in Figure 7 seen on page 15183 a linear relationship between CN- concentration and RGB color of the images over the concentration range is observed. On page 15178 column 2 in the Image Analysis section, it describes how fluorescent images of the solutions are captured with a smart phone camera under a 366 nm UV lamp where the images are imported into MATLAB and digitized using the “imread” function, and three output matrices of color values for red, green, and blue parts of the images are acquired.
Saiki is silent with regards to specific reagent, therefore, it would have been necessary and thus obvious to look to the prior art for conventional reagents. Shojaeifard provides this conventional teaching showing that it is known in the art to use GSH-AuNCs/Cu(PcTs) probes. Therefore, it would have been obvious to one having ordinary skill in the art to make the reagent of Saiki be the GSH-AuNCs/Cu(PcTs) probes because it is taught by Shojaeifard that these probes are effective for monitoring CN- ion in human blood serum, and that it is desirable to detect cyanide due to its toxicity (Shojaeifard; page 15177 column 1 paragraph 1, page 15178 column 1 paragraph 4).
Examiner further finds that the prior art included each element claimed (as set forth above), although not necessarily in a single prior art reference, with the only difference between the claimed invention and the prior art being the lack of actual combination of the elements within a single reference. Moreover, an ordinarily skilled artisan could have combined the elements as claimed by known methods (e.g., using the GSH-AuNCs/Cu(PcTs) probes with the analysis device), and that in combination, each element merely would have performed the same function as it did separately (i.e., change color in response to cyanide ion, and separate blood into plasma for interaction with reagent), and an ordinarily skilled artisan would have recognized that the results of the combination were predictable.
Therefore, pursuant to MPEP §2143 (I), Examiner concludes that it would have been obvious to an ordinarily skilled artisan to combine the analysis device of Saiki with the GSH-AuNCs/Cu(PcTs) probes of Shojaeifard, since the result would have been predictable.
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention for the gold nanocluster to have a size of 3 nm since the claimed ranges and the prior art ranges are close enough that one skilled in the art would have expected them to have the same properties, MPEP §2131.03 (III), and further being motivated to have the gold nanoclusters be 3 nm because Shojaeifard teaches that this is an effective size for gold nanoclusters.
Further, it would have been obvious to one skilled in the art to modify the photodetector of Saiki to be the smart phone camera, and to modify the analysis apparatus such that it includes MATLAB for digitizing the images and calculating a calibration curve as taught by Shojaeifard because Shojaeifard teaches that these components are effective for determining the concentration of CN- anions using the AuNCs/Cu(PcTs) probes, and because the determination of low levels of CN- is of significant importance (Shojaeifard; page 15177 column 1 paragraph 1).
Please note that the limitations “at least one electronic device (5) which is configured to enable to capture image for the purpose of determination of fluorescent colors of the combination of gold nanoclusters (4) and the cyanide-containing plasma under UV light in order to determine the amount of cyanide in the blood plasma under examination” and “at least one application (6) which is executed on the electronic device (5) and configured to determine the amounts of cyanide corresponding to the colors in the images captured by the electronic device (5).” are directed to the function of the apparatus and/or the manner of operating the apparatus, all the structural limitations of the claim has been disclosed by Shojaeifard and the apparatus of Shojaeifard is capable of enabling to capture image under UV light to determine amount of cyanide in blood plasma and capable of determining the amounts of cyanide corresponding to colors in the images. As such, it is deemed that the claimed apparatus is not differentiated from the apparatus of Shojaeifard (see MPEP §2114).
Please note that the blood sample, and therefore the plasma, and the UV light, have not been positively recited in the claim and is therefore not a part of the claimed system.
While Shojaeifard does teach GSH-AuNCs, Shojaeifard does not specify how many gold atoms are in the cluster.
In the analogous art of ligand-protected gold nanoclusters, Combes teaches Au15SG13, where SG is for glutathione (Combes; abstract).
Shojaeifard is silent with regards to specific amount of gold atoms in the GSH-AuNCs, therefore, it would have been necessary and thus obvious to look to the prior art for conventional gold atom amounts. Combes provides this conventional teaching showing that it is known in the art for GSH-AuNCs to have 15 gold atoms. Therefore, it would have been obvious to one having ordinary skill in the art to make the GSH-AuNCs of Shojaeifard have 15 gold atoms as taught by Combes because Combes teaches that this is an effective number of gold atoms for this specific type of gold nanocluster that uses glutathione as its ligand.
If it is determined that Shojaeifard does not teach that the gold nanoclusters having a size of 3-5 nm, in the analogous art of gold nanoclusters, Yang teaches where gold nanoclusters have a broad particle size distribution ranging from 0.5 to 5.4 nm with an average core diameter of 2.1 ± 1.1 nm (Yang; page 958 column 1 paragraph 1).
It would have been obvious to one skilled in the art to modify the size of the gold nanoclusters such that they have a core size with a diameter of 2.1 ± 1.1 nm as taught by Yang because it is taught by Halawa that the fluorescence of gold nanoclusters is size-dependent, where different emission colors from ultraviolet to near infrared can be achieved by modulating core size (Halawa; page 9 column 2 paragraph 2 into page 10 column 1).
Because Shojaeifard describes a red/blue shift depending on cyanide concentration, one skilled in the art would be motivated to modify the size of the gold nanoclusters as taught by Yang and Halwara in order to modulate the red/blue shift, where one skilled in the art would find it obvious that changing the size would allow for things such as a more distinct red color and/or more distinct color changes.
The claimed range overlaps or falls within the prior art range; in cases where the claimed range overlaps or falls within the prior art range, a prima facie case of obviousness of the range exists. It would have been obvious to one having ordinary skill in the art to have selected the portion of the gold nanocluster size in the range that corresponds to the claimed range. See MPEP 2144.05(I).
Regarding claim 29, modified Saiki teaches a system according to claim 1.
The limitations of claim 29 are directed to the function of the apparatus and/or the manner of operating the apparatus, all the structural limitations of the claim has been disclosed by modified Saiki and the apparatus of modified Saiki is capable of enabling the images of cyanide-containing sample to be captured under UV light. As such, it is deemed that the claimed apparatus is not differentiated from the apparatus of modified Saiki (see MPEP §2114).
Further, please note that the cyanide-containing samples nor UV light have been positively recited, and are therefore not a part of the claimed system.
The photodetector of Saiki has been modified to be the smart phone camera of Shojaeifard, where Shojaeifard does describe in the Image Analysis section on page 15178 column 2 that fluorescent images of solutions are captured with a smart phone camera under a 366 nm UV lamp.
Regarding claim 31, modified Saiki teaches a system according to claim 1. Shojaeifard further teaches characterized by the application which is executed on the electronic device and determines the cyanide concentration in the sample from the color data in the image by ensuring that the images captured by the electronic device are evaluated according to the colors stored in the database within the application and the cyanide reference values corresponding to these colors.
As described on page 15178 column 2 in the Image Analysis section of Shojaeifard, it describes that for each picture three data matrices composed of color values R, G, B are obtained, where these matrices are obtained from recorded images of the AuNCs/Cu(PcTs) probes with CN-. As such, the colors obtained from the images and analyzed in MATLAB will be according to RGB, where RGB are the colors stored within MATLAB. Further, as described on page 15182 in the Colorimetric Determination section of Shojaeifard a calibration curve is created where the calibration curve is understood to be formed by cyanide reference values, and that the calibration curve allows for subsequent CN- concentration determination in other samples.
Claim(s) 4, 8, 10, 12-16, 18, 20, 23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Saiki (US-2009/0246082-A1), Shojaeifard et al. “Efficient On-Off Ratiometric Fluorescence Probe for Cyanide Ion Based on Perturbation of the Interaction between Gold Nanoclusters and a Copper(II)-Phthalocyanine Complex” herein Shojaeifard, and Combes et al. “Functionalized Au15 nanoclusters as luminescent probes for protein carbonylation detection” herein Combes, and under the alternative rejection of Yang in view of Halawa, and in further view of Cho (US-2010/0009431-A1).
Regarding claim 4, Saiki teaches a system according to Claim 1. Saiki teaches where there are two substrates 1 and 2 that make up the analysis device 101 that are made of plastic and that they may be bonded using an adhesive agent (Saiki; [0059], [0062]). Saiki does not teach:
characterized by the compact disc (2) which comprises three polymethylmethacrylate (PMMA) layers -namely the top (21), the middle (23) and the bottom (25) one- and double-sided tape layers with adhesive properties -namely, the first adhesive (22) and the second adhesive (24)- to be placed between these layers (21, 23, 25).
In the analogous art of cartridges containing a reagent, Cho teaches a microfluidic device that has a platform (Cho; [0003], [0054]).
Specifically, Cho teaches where a platform is made of a plastic material, such as polymethyl methacrylate (PMMA) and may have either a two-layer structure or a three-layered structure (Cho; [0054], Figures 2-3). As described for Figure 3 showing the three-layered structure, the device includes a bottom plate 11, top plate 12, and partitioning/intermediate plate 13, where partitioning/intermediate plate 13 defines a portion for storing a fluid and a channel through which the fluid flows (Cho; [0054]). Additionally, the three plates can be bonded together via double-sided tape or an adhesive, or by fusing using ultrasonic waves (Cho; [0054]).
Examiner further finds that the prior art contained a device/method/product (i.e., assay device) which differed from the claimed device by the substitution of component(s) (i.e., assay device being made of two layers of plastic bonded with an adhesive agent) with other component(s) (i.e., the assay device having three layers of PMMA bonded via double-sided tape), and the substituted components and their functions were known in the art as above set forth. An ordinarily skilled artisan could have substituted one known element with another (i.e., a two layer assay device made of plastic bonded with an adhesive agent for a three layer assay device made of PMMA bonded with double-sided tape), and the results of the substitution (i.e., formation of channels and chambers for a sample) would have been predictable.
Therefore, pursuant to MPEP §2143 (I), Examiner concludes that it would have been obvious to an ordinarily skilled artisan to substitute the two layers of plastic bonded with an adhesive agent of reference Saiki with three layers of PMMA bonded with double-sided tape of reference Cho, since the result would have been predictable.
Regarding claim 8, modified Saiki teaches a system according to Claim 4. The analysis device of Saiki has been modified by Cho such that there will now be three layers of PMMA. [0054] of Cho describes that a portion for storing a fluid and a channel through which fluid flows is defined by the partitioning plate 13. Therefore, the various chambers and channels seen in Figure 19 of Saiki will be formed in the middle PMMA layer.
Saiki further teaches five different chambers- namely, the filling (fluid storage chamber 9), the separation (separation chamber 10), the pneumatic (solution component holding channel 36), the plasma collection (measurement cell 37) and the comparison chamber (measurement cell 28) (Saiki; [0195], Figure 19).
Regarding claim 10, modified Saiki teaches a system according to Claim 8. As described in claim 8 supra, the channels and chambers seen in Figure 19 of Saiki are now in the middle PMMA layer.
Saiki further teaches characterized by the compact disc (101) which comprises the middle PMMA layer with a second channel that carries the plasma-passing through the channel (joint channel 34) from the separation chamber (10) to the pneumatic chamber (36) during the centrifugation process being carried out for the separation process- from the pneumatic chamber (36) to the plasma collection chamber (37) (Saiki; [0195], Figure 19 where the connection between the solution component holding channel 36 to the measurement cell 37 is the second channel).
Please note that the plasma has not been positively recited in the claim and is therefore not a part of the claimed system.
Regarding claim 12, modified Saiki teaches a system according to Claim 8. As described in claim 8 supra, the channels and chambers seen in Figure 19 of Saiki are now in the middle PMMA layer.
Saiki further teaches characterized by the compact disc (101) which comprises the middle PMMA layer with the filling chamber (9) configured to be the place wherein the sample desired to be analyzed is dripped (Saiki; [0195] see fluid storage chamber 9 in which a sample solution of an amount required for analysis is injected and stored).
The limitation “the filling chamber (231) configured to be the place wherein the sample desired to be analyzed is dripped in order to determine the cyanide content” is directed to the function of the apparatus and/or the manner of operating the apparatus, all the structural limitations of the claim has been disclosed by modified Saiki and the apparatus of modified Saiki is capable of having a sample dripped in the fluid storage chamber. As such, it is deemed that the claimed apparatus is not differentiated from the apparatus of modified Saiki (see MPEP §2114).
Please note that Saiki has been modified with Shojaeifard to have the AuNCs/Cu(PcTs) probes that will detect cyanide.
Further, the sample has not been positively recited in the claim and is therefore not a part of the claimed system.
Regarding claim 13, modified Saiki teaches a system according to Claim 8. As described in claim 8 supra, the channels and chambers seen in Figure 19 of Saiki are now in the middle PMMA layer.
As described by [0195] of Saiki the fluid storage chamber 9 has sample solution injected and stored, where this chamber is now formed by the middle layer and thus the middle layer will be the place where sample is sent before the centrifugation process.
The limitation “the middle PMMA layer (23) configured to be the place wherein the sample to be analyzed is sent before the centrifugation process.” is directed to the function of the apparatus and/or the manner of operating the apparatus, all the structural limitations of the claim has been disclosed by modified Saiki and the apparatus of modified Saiki is capable of having the middle layer be the place where sample to be analyzed is sent before centrifugation. As such, it is deemed that the claimed apparatus is not differentiated from the apparatus of modified Saiki (see MPEP §2114).
Further, the sample has not been positively recited in the claim and is therefore not a part of the claimed system.
Regarding claim 14, modified Saiki teaches a system according to Claim 8. As described in claim 8 supra, the channels and chambers seen in Figure 19 of Saiki are now in the middle PMMA layer.
Saiki further teaches characterized by the compact disc (101) which comprises the middle PMMA layer with pneumatic chamber (36) configured to be the place wherein the plasma separated from the blood, that is the biological sample, is collected during the centrifugation-process of the sample to be analyzed (Saiki; [0195] see solution component holding channel 36 for holding a part of the solution component that is separated in the separation chamber 10, Figure 19).
The limitation “the middle PMMA layer (23) with pneumatic chamber (233) configured to be the place wherein the plasma separated from the blood, that is the biological sample, is collected during the centrifugation-process of the sample to be analyzed.” is directed to the function of the apparatus and/or the manner of operating the apparatus, all the structural limitations of the claim has been disclosed by modified Saiki and the apparatus of modified Saiki is capable of having the solution component holding channel in the middle layer be the place where plasma separated from blood is collected during centrifugation. As such, it is deemed that the claimed apparatus is not differentiated from the apparatus of modified Saiki (see MPEP §2114).
Please note that the biological sample has not been positively recited in the claim, and is therefore not a part of the claimed system.
Regarding claim 15, modified Saiki teaches a system according to Claim 8. As described in claim 8 supra, the channels and chambers seen in Figure 19 of Saiki are now in the middle PMMA layer.
Saiki further teaches characterized by the compact disc (101) which comprises the middle PMMA layer with the plasma collection chamber (37) configured to be the place wherein the plasmas that are collected in the pneumatic chamber (36) (Saiki; [0195] see measurement cell 37 for holding the solution component filled in the solution component holding channel 36).
Additionally, Saiki has been modified by Shojaeifard to have the AuNCs/Cu(PcTs) probes. [0196] of Saiki describes the reagent to be reacted with the solution component is held in the measurement cell 37. As such, the measurement cell 37 is where the plasma and AuNCs/Cu(PcTs) probes will be mixed.
The limitation “the plasma collection chamber (234) configured to be the place wherein the plasmas that are collected in the pneumatic chamber (233) by being separated from the blood by AuNCs are mixed with each other.” is directed to the function of the apparatus and/or the manner of operating the apparatus, all the structural limitations of the claim has been disclosed by modified Saiki and the apparatus of modified Saiki is capable of having the measurement cell be the place where plasma and AuNCs/Cu(PcTs) probes are mixed. As such, it is deemed that the claimed apparatus is not differentiated from the apparatus of modified Saiki (see MPEP §2114).
Further, the plasma has not been positively recited in the claim, and is therefore not a part of the claimed system.
Regarding claim 16, modified Saiki teaches a system according to Claim 8. As described in claim 8 supra, the channels and chambers seen in Figure 19 of Saiki are now in the middle PMMA layer.
Saiki has been modified by Shojaeifard to have the AuNCs/Cu(PcTs) probes. [0195] of Saiki describes that the measurement cell 37 hold the solution component filled in the solution component holding channel 36 and then mixing/reacting the solution component with reagent. [0196] of Saiki describes the reagent to be reacted with the solution component is held in the measurement cell 37.
Regarding claim 18, modified Saiki teaches a system according Claim 8. As described in claim 8 supra, the channels and chambers seen in Figure 19 of Saiki are now in the middle PMMA layer.
Saiki further teaches characterized by the compact disc (101) which comprises the middle PMMA layer with the comparison chamber (28) (Saiki; [0195], Figure 19).
The limitation “the comparison chamber (235) configured to contain a mixture of buffer solution and AuNC solution.” is directed to the function of the apparatus and/or the manner of operating the apparatus, all the structural limitations of the claim has been disclosed by modified Saiki and the apparatus of modified Saiki is capable of having the measurement cell hold a mixture of buffer solution and AuNC solution. As such, it is deemed that the claimed apparatus is not differentiated from the apparatus of modified Saiki (see MPEP §2114).
Further, please note that the buffer solution nor the AuNC solution have been positively recited, and are therefore not parts of the claimed system.
Regarding claim 20, modified Saiki teaches a system according to Claim 8. As described in claim 8 supra, the channels and chambers seen in Figure 19 of Saiki are now in the middle PMMA layer.
Saiki further teaches characterized by the compact disc (101) which comprises the middle PMMA layer with the comparison chamber (28) (Saiki; [0195], Figure 19).
The limitation “the comparison chamber (235) configured to enable the composition of plasma and AuNC in the plasma collection chamber (234) to be compared with the fluorescent color emitted by AuNCs that do not comprise plasma.” is directed to the function of the apparatus and/or the manner of operating the apparatus, all the structural limitations of the claim has been disclosed by modified Saiki and the apparatus of modified Saiki is capable of enabling the comparison of plasma in the measurement cell 37 to be compared with fluorescent color emitted by AuNCs that do not comprise plasma. As such, it is deemed that the claimed apparatus is not differentiated from the apparatus of modified Saiki (see MPEP §2114).
[0195] of Saiki describes measurement cell 28 for holding a mixed solution and for measuring the absorbance, turbidity, or number of cells in the mixed solution, and [0229] describes where hemoglobin concentration in the blood can be calculated by measuring the absorbance of diluted hemoglobin in measurement cell 28. Therefore, the sample to be measured in measurement cell 28 will not have any plasma. Further, it is understood from [0195] and [0196] of Saiki that a reagent will be in both measurement cell 37 and measurement cell 28. The reagent of Saiki has been modified by Shojaeifard to be the AuNC/Cu(PcTs) probes.
Further, please note that the plasma has not been positively recited in the claim, and is therefore not a part of the claimed system.
Regarding claim 23, modified Saiki teaches a system according to Claim 8. As described in claim 8 supra, Saiki is now a three layered device.
[0198] of Saiki describes sample solution is injected from injection port 8 and [0218] describes an injection port 21 that are both seen in Figure 19. Further seen in Figure 19 of Saiki are air holes 18, 19, 20, 35 (Saiki; [0178], [0213], [0215]).
As Saiki has been modified to now be a three layered device, one skilled in the art would find it obvious that the PMMA layer will have these openings. Additionally one skilled in the art would find it obvious that the openings would be in the uppermost of the three layers in order to reach the components of the middle layer, however the uppermost layer may be considered the bottom layer in the instance where the device is oriented upside-down.
The limitation “holes that allow the blood sample to be filled for cyanide detection, and ventilation holes in order to adjust the required pressure and to prevent the formation of air bubbles during filling.” are directed to the function of the apparatus and/or the manner of operating the apparatus, all the structural limitations of the claim has been disclosed by modified Saiki and the apparatus of modified Saiki is capable allowing blood sample to be filled and adjusting the required pressure and to prevent the formation of air bubbles during filling. As such, it is deemed that the claimed apparatus is not differentiated from the apparatus of modified Saiki (see MPEP §2114).
Please note that the blood sample has not been positively recited, and is thus not a part of the claimed system.
Claim(s) 32 is/are rejected under 35 U.S.C. 103 as being unpatentable over Saiki (US-2009/0246082-A1), Shojaeifard et al. “Efficient On-Off Ratiometric Fluorescence Probe for Cyanide Ion Based on Perturbation of the Interaction between Gold Nanoclusters and a Copper(II)-Phthalocyanine Complex” herein Shojaeifard, and Combes et al. “Functionalized Au15 nanoclusters as luminescent probes for protein carbonylation detection” herein Combes, and under the alternative rejection Yang in view of Halawa, and in further view of translated Fang (CN-113310959-A) herein Fang.
Regarding claim 32, modified Saiki teaches a system according to Claim 31. Shojaeifard teaches the use of MATLAB to output matrices of color values for red, green, and blue (Shojaeifard; page 15178 column 2 Analysis section). Therefore, Saiki in view of Shojaeifard do not teach the Color Grab application.
In the same problem solving area of obtaining standard curves for concentration and color intensity for an analyte, Fang teaches the use of Color Grab (Fang; [n0004], [n0012]).
Specifically, Fang teaches where free apps such as Color Grab has the system’s colors converted into a color space model, where commonly used color spaces include RGB and Lab (Fang; [n0004]). As further described in [n0035], an Android phone with Color Grab software is used to obtain RGB color intensities in a series of solutions as they gradually fade, where a linear relationship between value changes and concentration of ascorbic acid is created.
Examiner further finds that the prior art contained a device/method/product (i.e., analysis apparatus) which differed from the claimed device by the substitution of component(s) (i.e., MATLAB software) with other component(s) (i.e., Color Grab software), and the substituted components and their functions were known in the art as above set forth. An ordinarily skilled artisan could have substituted one known element with another (i.e., MATLAB software switched with Color Grab), and the results of the substitution (i.e., determination of color intensity differences when measuring the concentration of an analyte) would have been predictable.
Therefore, pursuant to MPEP §2143 (I), Examiner concludes that it would have been obvious to an ordinarily skilled artisan to substitute MATLAB of reference Shojaeifard with Color Grab of reference Fang, since the result would have been predictable.
From [n0004] of Fang, it describes where a common color space is Lab where one skilled in the art would find it obvious that therefore values would be presented through the L*a*b* color system.
Other References Cited
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Qian et al. “Quantum Sized Gold Nanoclusters with Atomic Precision” describes in the abstract that atomically precise nanoclusters are represented by molecular formulas such as Aun(SR)m for thiolate-protected ones, where n and m denote the respective number of gold atoms and ligands. SR being for thiolate.
Conclusion
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/S.Y.L./Examiner, Art Unit 1796
/MELVIN C. MAYES/Supervisory Patent Examiner, Art Unit 1759
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