The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1, 5, 12-13, 16, 19-24, 26, 28-30, 39, 45, 49, 52, and 55 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. With respect to claim 1, the structural relationship between the first array of electrodes and the printed circuit board is not clear. Are the electrodes simply fabricated as conductive pads on the printed circuit board or is there also electrical circuitry connecting the electrodes to something else? Similarly, the structural relationship between the second array of electrodes and the semiconductor layer is not clear. Are the electrodes simply fabricated as conductive pads on the semiconductor layer, is the semiconductor layer simply a covering/supporting layer of semiconductor material either deposited on or below the electrodes or is there electrical circuitry within the semiconductor layer connecting the electrodes to something else? With respect to claim 5, is the CMOS layer simply a layer of semiconductor material produced through a CMOS process or does it include circuitry/electrical components produced by the CMOS process? With respect to claim 12, there are several ways in which an electrode array could be “larger” than another electrode array: number of electrodes in the array, area of the arrays and size of the electrodes in the array. Thus it is not clear what applicant is attempting to claim by requiring the first array of electrowetting electrodes to be “larger” that the second array of electrowetting electrodes. Claim 13 has a similar problem. With respect to claim 16, Instant paragraph [0171] teaches that in TFT (thin-film transistors), individual transistors (i.e., CMOS) are fabricated underneath each electrode (i.e., pixel) enabling electronics, such as switches and sensors, to be embedded at each electrode location. Since that appears to require a CMOS layer, it is not clear if applicant is requiring the array of the first array of electrowetting electrodes to be a CMOS layer on the printed circuit board or if applicant is actually referring to the second array of electrowetting electrodes because they require a semiconductor layer (claim 1) that is required to be a CMOS layer (claim 5). With respect to claim 19, the structural relationship between the array of nanofeatures and other elements such as the first and second arrays of electrowetting electrodes is not clear. Is there a positioning relationship between the nanofeatures and individual electrodes in either of the electrowetting arrays? Claims 20-24, 26, and 28-30 are dependent from one or more of the above claims and fail to correct the above outlined clarity issues of the claim(s) from which they depend. With respect to claim 39, the substrate surface comprises the first contact electrically coupled to a first electrode and a second contact electrically coupled to a second electrode. The also requires that the substrate surface comprises a digital microfluidic device. Examiner notes that there is no clear structure required for the digital microfluidic device so that its structure and its structural relationship to the first contact electrically coupled to a first electrode and a second contact electrically coupled to a second electrode are undefined. Claims 45, 49, 52, and 55 are dependent from claim 39 and fail to correct the above outlined clarity issues of the claim.
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.
Claims 1 and 12-13 are rejected under 35 U.S.C. 103 as being unpatentable over Pollack (US 2013/0059366) in view of Liu (US 2021/0060547). In the patent publication Pollack teaches a droplet actuator device and methods for integrating gel electrophoresis analysis with pre or post-analytical sample handling as well as other molecular analysis processes. Using digital microfluidics technology, the droplet actuator device and methods of the invention provide the ability to perform gel electrophoresis and liquid handling operations on a single integrated device. The integrated liquid handling operations may be used to prepare and deliver samples to the electrophoresis gel, capture and subsequently process products of the electrophoresis gel or perform additional assays on the same sample materials which are analyzed by gel electrophoresis. In one embodiment, one or more molecular assays, such as nucleic acid (e.g., DNA) quantification by real-time PCR, and one or more sample processing operations such as sample dilution is performed on a droplet actuator integrated with an electrophoresis gel. In one embodiment, an electrophoresis gel may be integrated on the top substrate of the droplet actuator. Paragraphs [0039]-[0041] teach that Figure 1 illustrates a side view of a portion of an integrated droplet actuator 100 for gel electrophoresis. Droplet actuator 100 may include a bottom substrate 110 and a top substrate 112 that are separated by a gap 114. Bottom substrate 110 may be attached to top substrate 112 by an epoxy glue ring 116. Gap 114 may be filled with a filler fluid, such as silicone oil (not shown). Bottom substrate 110 may include a path or array of droplet operations electrodes 118 (e.g., electrowetting electrodes). Bottom substrate 110 may, for example, be formed of a printed circuit board (PCB). Top substrate 112 may, for example, be formed of a plastic material with high transparency and low fluorescence in the wavelength range compatible with fluorescence detection (i.e., suitable for fluorimeter operation). For example, top substrate 112 may be formed of cyclo-olefin polymer (COP) and/or copolymer (COC). A hydrophobic layer 120 may be disposed on the surface of bottom substrate 110 that is facing gap 114 (i.e., atop droplet operations electrodes 118). Similarly, another hydrophobic layer 120 may be disposed on the surface of top substrate 112 that is facing gap 114. With respect to claim 1, Figure 1 with its associated discussion teach a droplet manipulation device comprising: a first substrate comprising: a first layer comprising a first array of electrowetting electrodes and a printed circuit board; and a second substrate separated from the first substrate, forming a droplet operations gap between the first substrate and the second substrates. Pollack does not teach a second layer superior to a region of the first layer, wherein the second layer comprises a second array of electrowetting electrodes and a semiconductor layer.
With respect to claim 1, Liu teaches a micro-fluidic substrate, a micro-fluidic structure and a driving method thereof. The micro-fluidic substrate includes a substrate, and a plurality of driving electrodes on the substrate and configured to drive a droplet to move, the plurality of driving electrodes being in a same layer with a gap space between adjacent driving electrodes. The micro-fluidic substrate further includes: at least one auxiliary electrode on the substrate and configured to drive the droplet to move, an orthographic projection of the auxiliary electrode on the substrate at least partially overlapping with an orthographic projection of the gap space on the substrate, and the auxiliary electrode and the driving electrodes being in different layers. Paragraphs [0059]-[0060] described Figure 1 as a conventional micro-fluidic structure including two opposing substrates, one of which is provided with an array of driving electrodes 51, the other of which is provided with a common electrode 52. Two respective sides of the two substrates, that face each other, are each provided with a lyophobic layer 99 (i.e., a layer having lyophobicity to a droplet), and the droplet 9 is between the two lyophobic layers 99. When a predetermined common voltage is applied to the common electrode 52, a predetermined driving electric field can be caused at and around the droplet 9 by applying different driving voltages to the driving electrodes 51 at different positions relative to the droplet 9, which causes specific deformation and movement of the droplet 9, thereby controlling the droplet 9. It is noted that, in order to avoid the electric conduction between different driving electrodes 51, there is a gap space 59 between adjacent driving electrodes 51, and no electric field is formed at the gap space 59. Therefore, if the gap space 59 is too large, the droplet 9 cannot move continuously during the movement of the droplet 9, and if the gap space is too small, adjacent driving electrodes 51 are liable to be electrically coupled, which results in failure of the fabricated micro-fluidic structure. Paragraph [0064] teaches that in the micro-fluidic substrate of this invention, the auxiliary electrode capable of driving the droplet to move is disposed at the gap space between the driving electrodes. The auxiliary electrode and the driving electrodes are in different layers, and thus the auxiliary electrode and the driving electrodes may overlap with each other. Therefore, the driving electric field can be formed at the gap space between the driving electrodes, thereby eliminating or reducing the space where the driving electric field cannot be formed, and controlling the droplet more smoothly.
It would have been obvious to one of ordinary skill in the art at the time the application was filed to add auxiliary electrodes in a separate layer of the first substrate as taught by Liu to the Pollack device because of the ability to control the droplet movement more smoothly as taught by Liu. With respect to claims 12-13, Figure 10 of Liu shows a structure in which each driving electrode 51 is lager in size than each auxiliary electrode 6. The size appears to be greater than 1.5 times so that modification of Pollack with Liu would meet the limitations of claims 12-13 for the reasons given above for claim 1.
Claims 39, 45, 49, 52, and 55 are rejected under 35 U.S.C. 103 as being unpatentable over Merriman (US 2016/0340220) in view of Choi (Lab on a Chip 2012). In the patent publication, with respect to claim 39, Merriman teaches a molecular sensor for direct detection of a single molecule target (para [0040]- In various embodiments, a single molecule biosensor device), the molecular sensor comprising a substrate surface comprising: (a) a first contact (Fig 1, element 106) electrically coupled to a first electrode (Fig 1, element 102) (para [0041]- FIG. 1 illustrates a schematic representation of a sensor device 100 comprising a sensor 101 in accordance with various embodiments. Sensor 101 includes a first electrode 102 Sensor 101 can further comprise a sensor complex 105 functionally coupled to the first electrode 102 and the second electrode 103. In various embodiments, the sensor complex may be coupled to the electrodes via first contact 106); (b) a second contact (Fig 1, element 107) electrically coupled to a second electrode (Fig 1, element 107) (para [0041]- FIG. 1 illustrates a schematic representation of a sensor device 100 comprising a sensor 101 in accordance with various embodiments. Sensor 101 includes a second electrode 103 Sensor 101 can further comprise a sensor complex 105 functionally coupled to the first electrode 102 and the second electrode 103. In various embodiments, the sensor complex may be coupled to the electrodes via second contact 107); wherein (i) the first and second electrodes are separated by a sensor gap (para [0040]- The first electrode and the second electrode are separated by a sensor gap defined by the electrodes and/or contacts attached to the electrodes) and (ii) the sensor gap is spanned by a bridge molecule such that interaction of the bridge molecule with the targeted single molecule generates a detectable electrical signal (para [0040]- The first and second electrodes can be coupled by a bridge molecule spanning the sensor gap The bridge molecule attachment to the electrodes may be mediated by a contact. A probe molecule or molecular complex can be coupled to the bridge molecule. The probe can be a biomolecule such as an enzyme configured to interact with a single target molecule; para [0041]- For example, as illustrated in FIG. 1, sensor complex 105 may interact with a target molecule 108 such as a DNA molecule, and the sensor device can be used to detect the presence of and/or properties of the target molecule). Referring to claim 41, Merriman teaches the molecular sensor of claim 39. Merriman further teaches wherein the substrate comprises a silicon substrate comprising integrated microelectronics (para [0049]- For example, sensor device 200 can comprise a silicon nitride layer 260 overlying a silicon dioxide layer 261. Sensor device 200 can further comprise buried gate 204 underlying the semiconductor substrate layer(s) on which the electrodes are disposed. The various components described above can be fabricated on a support such as a silicon chip 263; para [0082]- multiple pairs of electrodes in parallel at high density and with highly precise physical specifications in a process amenable to commercial-scale production of sensor devices using CMOS fabrication and/or other microelectronic fabrication methods). Merriman does not teach that the substrate surface comprises a digital microfluidic device.
In the paper Choi teaches a new platform for lab-on-a-chip system that utilizes a biosensor array embedded in a digital microfluidic device. With field effect transistor (FET)-based biosensors embedded in the middle of droplet-driving electrodes, the proposed digital microfluidic device can electrically detect avian influenza antibody (anti-AI) in real time by tracing the drain current of the FET-based biosensor without a labeling process. Digitized transport of a target droplet enclosing anti-AI from an inlet to the embedded sensor is enabled by the actuation of electrowetting-on-dielectrics (EWOD). A reduction of the drain current is observed when the target droplet is merged with a pre-existing droplet on the embedded sensor. This reduction of the drain current is attributed to the specific binding of the antigen and the antibody of the AI. The proposed hybrid device consisting of the FET-based sensor and an EWOD device, built on a coplanar substrate by monolithic integration, is fully compatible with current fabrication technology for control and read-out circuitry. Such a completely electrical manner of inducing the transport of bio-molecules, the detection of bio-molecules, the recording of signals, signal processing, and the data transmission process does not require a pump, a fluidic channel, or a bulky transducer. Thus, the proposed platform can contribute to the construction of an all-in-one chip.
With respect to claim 39, it would have been obvious to one of ordinary skill in the art at the time the application was filed to incorporate the Merriman sensor into digital microfluidic device such as taught by Choi because of the ability to electrically detect an analyte in real time by tracing the drain current of the FET-based biosensor without a labeling process.
With respect to claims 45, 49, 52, and 55, paragraph [0051] describes the sensor shown in figure 3 and teaches that sensor 301 further comprises sensor complex 305. In various embodiments, a sensor complex 305 can comprise a bridge molecule 333 and a probe 334. Probe 334 can be coupled to bridge molecule 333 via a linker 337, which here is shown as a streptavidin-biotin complex, with the biotin covalently incorporated into a nucleotide of the DNA bridge 333, and the streptavidin chemically, covalently cross-linked to the polymerase 334. Each of the various components of sensor complex 305 are described in greater detail below. Paragraph [0052] teaches that a bridge molecule 333 can comprise a chemically synthesized bridge molecule or a biopolymer bridge molecule. A chemically synthesized bridge molecule or a biopolymer bridge molecule may be configured to span a sensor gap both structurally and functionally. For example, a chemically synthesized molecule or biopolymer molecule may be configured through selection and use of atomically precise molecular subunits (e.g., monomeric units for incorporation into a polymeric bridge molecule) that provide for construction of a bridge molecule with known or predictable structural parameters, incorporation of features that facilitate self-assembly to contact points and self-assembly of a probe molecule to a bridge molecule, as well as suitable electrochemical properties for electrical connection of electrodes. Paragraph [0054] teaches that the term “biopolymer” can include any molecule comprising at least one monomeric unit that can be produced by a living organism, although the actual monomeric unit comprising a biopolymer or the polymer itself need not be produced by an organism and can be synthesized in vitro. Examples of biopolymers include polynucleotides, polypeptides, and polysaccharides, including well known forms of these such as DNA, RNA and proteins. Bridge molecules that comprise a biopolymer can include multi-chain polymeric proteins in a simple “coiled-coil” configuration, as occurs in collagen proteins, or a more complex folding of heavy and light chain polymeric proteins, such as in immunoglobin molecules (e.g. IgG). Such complexes that comprise biopolymers also include common nucleic acid duplex helices, such as a DNA double helix, which is two DNA single strand molecules bound into a helical double strand by hydrogen bonding, PNA-PNA duplexes, as well as DNA-RNA, DNA-PNA, and DNA-LNA hybrid duplexes. A biopolymer molecule need not be naturally occurring or produced by an organism to be classified as a biopolymer. Instead, the term “biopolymer” can include molecules that are synthesized enzymatically as well as non-enzymatically and can likewise include molecules comprising synthetic analogues of naturally-occurring monomeric units. For example, biopolymers can comprise peptide nucleic acids (PNAs) and locked nucleic acids (LNAs), synthetic analogues of DNA and RNA that have enhanced stability properties. In addition, a biopolymer can comprise any of a variety of modifications that may be added to a molecule. The use of biopolymer bridge molecules can provide various benefits, including synthesis of precisely controlled structures having suitable size and chemistry for sensor function, they may be naturally compatible with the target molecules for the sensor (e.g., compatible with the same liquid buffer medium), and the biotech industry has developed extensive capabilities to design, engineer and synthesize such molecules, and to manufacture them economically and with high quality control. Paragraph [0056] teaches that a bridge molecule can comprise a linear biopolymer such as a double-stranded DNA helix or an α-helical polypeptide. As illustrated in FIG. 3, bridge molecule 333 comprises a linear biopolymer double-stranded DNA bridge molecule with a first end 334 coupled to first contact 306 and a second end 335 coupled to second contact 307. Paragraph [0059] teaches that a double-stranded DNA can comprise a thiol-modified oligo comprising a thiol-modified nucleotide or base. A thiol-modified nucleotide can comprise a self-assembling anchor configured to bind to a gold nanobead or similar surface contact. Subsequent paragraphs describe a variety of different bridging molecules, structures to bind them to the respective electrodes and probe structures so that claims 45, 49, 52, and 55 are taught by Merriman.
Examiner notes that several dependent claims are not rejected with art. However, the claims have significant clarity issues. For that reason, it is difficult to determine if it is possible to overcome the clarity issues. As such examiner indicates the possibility of obtaining an allowable claim if the dependent claim(s) are incorporated into an independent claim and all clarity issues of the independent and dependent claims are overcome.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. The additionally cited art is related to digital microfluidic structures.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Arlen Soderquist whose telephone number is (571)272-1265. The examiner can normally be reached 1st week Monday-Thursday, 2nd week Monday-Friday.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lyle Alexander can be reached at (571)272-1254. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ARLEN SODERQUIST/ Primary Examiner, Art Unit 1797
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