DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 76-79, 82-101 is/are rejected under 35 U.S.C. 103 as being unpatentable over Pamula et al ( (US 20070241068) in view of Guo, L. et al. "Dual-color plasmonic enzyme-linked immunosorbent assay based on enzyme-mediated etching of Au nanoparticles". Sci. Rep. 6, 2016, 32755, pp. 1-7.
Regarding claim 76, Pamula teach a digital microfluidic (DMF) device for performing a test for a target analyte, the DMF device comprising: a. a DMF cartridge comprising a bottom substrate and a top substrate separated by a droplet operations gap, wherein the bottom substrate comprises a plurality of droplet operations electrodes configured for performing droplet operations on a liquid droplet in the droplet operations gap (Para. 0453: two parallel substrates separated by a gap and an array of electrodes on one or both substrates); b. one or more reaction chambers or reaction zones on the bottom substrate that are supplied by an arrangement of the droplet operations electrodes, wherein each reaction chamber or reaction zone comprises at least one detection spot (Para. 0364; Fig. 17: detector area 1710) and is configured for performing a detection of surface plasmon resonance (Para. 0639) or ELISA (Para. 0008) and quantification of a target analyte in a droplet; and c. a controller coupled to the droplet operations electrodes and programmed to activate and deactivate the droplet operations electrodes and thereby effect droplet operations for performing the test (Para. 0452: controller to control the electrodes).
Pamula is silent to a plasmonic particle-assisted ELISA (pELISA) for detection.
Guo et al teach a plasmon based colorimetric ELISA with higher sensitivity than traditional ELISA (p. 1, Abstract and para. 2-3: plasmonic ELISA shows ultralow limit of detection with color changes visible to the naked eye). It is advantageous to provide the plasmon ELISA to ensure detectable color changes when the analytes are at different concentrations. Simple substitution of one known element for another to obtain predictable results is held to be obvious. Therefore, it would have been obvious to one of ordinary skill in the art to substitute the plasmonic ELISA of Guo for the plasmon and ELISA detections in Pamula to provide the above advantage of an ultrasensitive colorimetric detection visible to the naked eye.
Regarding claim 77, Pamula/Guo teach the top substrate further comprises one or more reagent wells for receiving a reagent container, wherein the one or more reagent wells are arranged in relation to one or more reagent reservoir electrodes on the bottom substrate (Pamula: Para. 0515: reagent wells; Para. 0364; Fig. 17: 1703: reagent reservoirs).
Regarding claim 78, Pamula/Guo teach the one or more reagent wells further comprise a reagent port arranged to permit flow of reagent fluids from a reagent container into the one or more reagent wells. (Pamula: Para. 0468-0469: cartridge)
Regarding claim 79, Pamula/Guo teach at least one reagent well comprises a two- port well comprising:i. a first input port comprising a luer port or sample port well for receiving and inputting a sample fluid (Pamula: Fig. 17: 1704); and ii. a second input port comprising a reagent container well for receiving and inputting a reagent fluid (Pamula: Fig. 17: 1703).
Regarding claim 82, Pamula/Guo teach comprising one or more magnets situated in sufficient proximity to the droplet operations gap to permit magnetic manipulation of magnetically responsive beads and/or particles in a droplet in the droplet operations gap. (Pamula: Para. 0171: magnet)
Regarding claim 83, Pamula/Guo teach a communications interface for connecting the DMF device to the controller and exchanging test information from the at least one detection spot with a remote computer processing unit (CPU), wherein the remote CPU is part of a smart device. (Pamula: Para. 0681: remote computer)
Regarding claim 84, Pamula/Guo teach the communications interface comprises a wired and/or wireless communication interface. (Pamula: Para. 0681: remote computer connected to the user's computer through a local area network)
Regarding claim 85, Pamula/Guo teach a system for performing a test for a target analyte, the system comprising: a. the DMF device of claim 76 (see rejection supra); and b. a test application for downloading onto a user device, wherein the test application provides a user interface for operating the system and/or the DMF device and instructions for performing a pELISA test for a target analyte, and wherein the test application further comprises: i. an algorithm for processing digital image data of the pELISA test to produce a colorimetric readout based on a colorimetric change (Pamula: Para. 0575-0579; Fig. 20: user interface display); and ii. an algorithm for analyzing the colorimetric readout to determine the presence or absence of a target analyte (Pamula: Para. 0600: software to analyzing a sample and outputting results).
Regarding claim 86, Pamula/Guo teach the DMF device of claim 76, and the method of performing a biological analysis for a target analyte, the method comprising: a. providing the DMF device of claim 76; providing a reaction surface and a capture molecule in the one or more reaction chambers or reaction zones in the droplet operations gap of the DMF device (Para. 0364; Fig. 17: detector area 1710) ; c. using droplet operations effected by the controller by: i. introducing a sample fluid onto the reaction surface, wherein the sample fluid potentially comprises a target analyte that binds to the capture molecule, forming a target-capture molecule complex immobilized on the reaction surface; ii. introducing a detection antibody onto the reaction surface, wherein: 1. an enzyme is conjugated to the detection antibody, and/or 2. the enzyme is conjugated to the capture molecule; iii. introducing a detection solution comprising an enzyme substrate onto the reaction surface, wherein in the presence of a target-capture molecule complex a colorimetric change is produced (Pamula: para. 0254-0256 substituted with the plasmonic ELISA in Guo Fig. 1) and d. measuring at the one or more detection spots in each of the one or more reaction chambers or reaction zones the colorimetric change in response to the enzyme catalyzed detection of the target analyte (Pamula: para. 0254-0256, 0364 detector area substituted with the plasmonic ELISA in Guo Fig. 1)
Regarding claim 87, Pamula/Guo teach the reaction surface comprises the capture molecule immobilized thereon, and the detection solution further comprises a plasmonic nanoparticle. (Guo: Fig. 1 )
Regarding claim 88, Pamula/Guo teach the plasmonic nanoparticle comprises a nanosphere, a nanorod, a nanourchin, or a nanostar (Guo: p. 1 para. 3: AuNP with diameter of 45nm quasi-spherical)
Regarding claim 89, Pamula/Guo teach the reporter antibody having affinity for a different epitope on the analyte (Pamula: Para. 0252: modified Pamula having the plasmon ELISA with the different reporter antibody, it is noted that the additional reporter antibody with a different epitope increasing the sensitivity and/or range of detection for a target analyte.)
Regarding claim 90, Pamula/Guo teach the plasmonic nanoparticle comprises a gold nanoparticle (Guo: Fig. 1 AuNP).
Regarding claim 91, Pamula/Guo teach the reaction surface comprises a substrate surface of the DMF device, a magnetically responsive bead, magnetic nanoparticles, gold nanoparticles, or latex beads (Guo: Fig. 1 AuNP).
Regarding claim 92, Pamula/Guo teach the capture molecule comprises an antibody, an antigen, or other receptor-ligand interactions (Pamula: Para. 0247: capture antibodies immobilized; Guo Fig. 1).
Regarding claim 93, Pamula/Guo teach the sample fluid comprises a bodily fluid from a human or an animal. (Para. 0067: biological specimens)
Regarding claim 94, Pamula/Guo teach the target analyte comprises two or more target analytes (Pamula: Para. 0287).
Regarding claim 95, Pamula/Guo teach the target analyte is a protein (Pamula: Para. 0018).
Regarding claim 96, Pamula/Guo teach the target analyte is a molecule or molecular structure from a virus, a bacterium, or any other pathogen, wherein the molecule or molecular structure (i) is bound to the outer surface of the virus, the bacterium, or the any other pathogen, or (ii) is internal to the virus, the bacterium, or the any other pathogen. (Para. 0096: DNA or RNA associated with bacteria, virus)
Regarding claim 97, Pamula/Guo teach the internal molecule or molecular structure is exposed by disrupting the integrity of the virus, the bacterium, or the any other pathogen. (Pamula: Para. 0146: cell lysis)
Regarding claim 98, Pamula/Guo teach the detection antibody comprises a primary antibody or a secondary antibody conjugated to an enzyme. (Guo: Fig. 1: secondary antibody conjugated to HRP-streptavidin)
Regarding claim 99, Pamula/Guo teach the enzyme comprises horseradish peroxidase (HRP) and the enzyme substrate comprises TMB. (Guo: Fig. 1: HRP and TMB)
Regarding claim 100, Pamula/Guo teach the detection solution further comprises a metal ion precursor (Guo: p. 1 para. 3:gold ions).
Regarding claim 101, Pamula/Guo teach the colorimetric change is caused by: (i) etching of the plasmonic nanoparticle in response to the enzyme catalyzed detection of the target analyte; (ii) aggregation of the plasmonic nanoparticle in response to the enzyme catalyzed detection of the target analyte; (iii) growth of the plasmonic nanoparticle in response to the enzyme catalyzed detection of the target analyte; or (iv) quenching and/or unquenching the fluorescence of a fluorescent probe in response to the enzyme catalyzed detection of the target analyte. (Pg. 1, para. 3: growth of AuNP to aggregated nanoparticles in presence of the analyte).
Claim(s) 80-81 is/are rejected under 35 U.S.C. 103 as being unpatentable over Pamula/Guo in view of Crivelli et al (US 20170152081).
Regarding claims 80-81, Pamula/Guo teach the reagent container is sealed pouch which is punctured or compressed to transfer the liquid into the droplet microactuator. (Para. 0499:sealed pouch punctured or compressed to transfer the liquid into the droplet microactuator) . Pamula/Guo are silent to the release mechanism attached to the top plate in proximity to the input second port for bursting the reagent container and releasing the reagent fluid; wherein the release mechanism comprises a pointed or sharp-edged feature. (Para. 0100: pointed tip)
Crivelli et al et al teach a digital microfluidics (Para. 0153) with reagent loading using a release mechanism attached to the top plate in proximity to the input second port for bursting the reagent container and releasing the reagent fluid; wherein the release mechanism comprises a pointed or sharp-edged feature. ( Para. 0100: piercer 118 to puncture the lid to open flow channel of reagents to the fluidics system; Fig. 2: 118). It is advantageous to provide a pointed release mechanism on the top plate to burst the reagent container and release the fluid to ensure the reagent enters the fluidic portion. Combining prior art elements according to known methods to yield predictable results is known. Therefore it would have been obvious to one of ordinary skill in the art to combine the piercer of Crivelli et al to provide the above advantage of using a pointed release mechanism to ensure the reagent enters the fluidic portion.
Claim(s) 102 is/are rejected under 35 U.S.C. 103 as being unpatentable over Pamula/Guo in view of Myers et al (US-20150286803).
Regarding claim 102, Pamula/Guo teach the analyzer can be a portable hand-held analyzer (Para. 0051; Fig. 19A). Pamula/Guo teach the method of performing a user conducted test for a target analyte, the method comprising: a. providing the system of claim 85 to a user (see rejection of claim 85 supra). Pamula/Guo teach c. introducing a user sample into one or more sample reservoirs of the DMF device (Para. 0449: loading samples), wherein the pELISA test is automatically performed to test for the presence or absence of the target analyte (Pamula: para. 0096 fully automated; Guo: Fig. 1); and d. capturing a digital image of the pELISA test results for automated analysis for determining the presence or absence of the target analyte (Pamula: Para. 0442: automated image analysis).
Pamula/Guo are silent to b. downloading the test application onto the user's smart device to initiate and set up the testing process, wherein setting up the testing process comprises: (i) establishing a communication link between the user's smart device and the DMF device and (ii) capturing an image of a QR code provided on the DMF device and collecting any other required test information.
Myers et al teach a microfluidic cartridge (Para. 0001) downloading the test application onto the user's smart device to initiate and set up the testing process, wherein setting up the testing process comprises: (i) establishing a communication link between the user's smart device and the DMF device and (ii) capturing an image of a QR code provided on the DMF device and collecting any other required test information. (Para. 0026: smartphone 200 uses QR code on the test device 100 that has test information 130). It is advantageous to set up the testing process using a QR code with the information of the test to ensure the analysis uses specific testing information such as test parameters for interpreting image data (Para. 0026). Combining prior art elements according to known methods to yield predictable results is known. Therefore it would have been obvious to one of ordinary skill in the art to combine the downloading the test application onto the user's smart device to initiate and set up the testing process, wherein setting up the testing process comprises: (i) establishing a communication link between the user's smart device and the DMF device and (ii) capturing an image of a QR code provided on the DMF device and collecting any other required test information of Myers to provide the above advantage of ensuring the analysis uses specific testing information such as test parameters for interpreting image data.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DENNIS MICHAEL WHITE whose telephone number is (571)270-3747. The examiner can normally be reached M-F 8:30am-5pm.
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/Dennis White/Primary Examiner, Art Unit 1758