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 § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-2, 6, 9-11 and 18-20 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jebrail et al. (US 2020/0061621) (Jebrail).
Regarding claim 1, Jebrail discloses a fluid processing device (abstract) comprising:
a first plate-like structure and a second plate-like structure configured to manipulate one or more droplets, which are located between the first and the second plate-like structure, by electrowetting (par [0073] [0076]); and
a plurality of functional zones (Fig. 9, par [0053] [0085]), wherein each functional zone comprises at least two of:
a first sub-zone for applying heat to the one or more droplets (par [0053] [0085]);
a second sub-zone for applying a magnetic field to the one or more droplets (par [0085]); and
a third sub-zone for providing light onto and/or detecting light emitted by the one or more droplets (Fig. 9, par [0085]).
Jebrail's disclosed heating regions correspond to the claimed first sub-zones, Jebrail's disclosed magnetic regions correspond to the claimed second sub-zones, and Jebrail's disclosed optically read/imaging regions correspond to the claimed third sub-zones. As shown in FIG. 9, these function-specific regions are distributed across the electrode array; respective larger regions of the array encompassing at least two different types of such regions correspond to the plurality of claimed functional zones, such that each mapped functional zone comprises at least two of the claimed sub-zone types.
Regarding claim 2, Jebrail discloses that wherein the functional zones are identical (par [0053] [0085]).
Jebrail discloses that “The drive electrodes under the secured dielectric may therefore form a plurality of unit cells (one drive electrode per unit cell), and each cell or region of cells (multiple cells) may be controlled to perform a specified function.” (par [0085]); “The different regions are indicated by different boxes, and may be distributed in a particular arrangement over the array.” (par [0053]); “Two central heating zones (one spanning five electrodes, the other spanning 32 electrodes) are also included, and may be thermally cycled over the entire zone or over regions of the zone(s).” (par [0053]); Fig. 9).
As mapped with respect to claim 1, Jebrail's heating regions and magnetic regions correspond to the claimed sub-zones, and larger regions of the electrode array encompassing at least two different such sub-zones correspond to the claimed functional zones. Fig. 9 discloses a regular array of repeating unit cells and multiple magnetic regions 603 together with heating zone 609. Two or more same-sized regions of that array, each encompassing a region of heating zone 609 and a magnetic region 603, correspond to identical functional zones. Jebrail expressly permits heating to occur over “regions of the zone(s),” such that the respective portions of heating zone 609 within the mapped functional zones correspond to respective first sub-zones.
Regarding claim 6, Jebrail further teaches that wherein in the second sub-zone, one or more magnetic field generating elements are respectively arranged on or besides an outer surface of the first plate-like structure or of the second plate-like structure (par [0082] [0085]). Jebrail teaches that “the reaction mixture ... was exchanged between the Purification Module and Transfer conduit three times while engaging an external magnet beneath the interface area, such that the beads were recovered from the reaction mixture by immobilizing them on the surface of the DMF device” (par [0082]); “One or more magnetic zones 603 may be used for turning on/off magnetic fields that may be useful to immobilize a magnetic particle”; “the magnet may be positioned right under the heating zone when using resistive heating.” (par [0085]).
Jebrail's external magnet corresponds to the claimed magnetic field generating element. The external magnet is positioned beneath the interface area/right under the functional zone of the DMF device and therefore is arranged beside an outer surface of the plate-like structure at the mapped magnetic sub-zone. Jebrail's DMF device has droplets between bottom and top plates, with actuation electrodes on or adjacent to the bottom plate.
Regarding claim 9, Jebrail further teaches wherein at least one of the functional zones comprises the first sub-zone, the second sub-zone, and the third sub-zone, and comprises a fourth sub-zone, which is identical to either the first sub-zone, the second sub-zone, or the third sub-zone (par [0053]).
Jebrail teaches that the different functional regions “may be distributed in a particular arrangement over the array,” and specifically teaches seven magnetic regions, two central heating zones, and four optically read zones (par. [0053]), “seven of the electrodes are configured as magnetic regions 605, which can apply a local (to that electrode) magnetic force to retain a magnetic bead or particle within a droplet on the electrode”; “Two central heating zones (one spanning five electrodes, the other spanning 32 electrodes) are also included, and may be thermally cycled over the entire zone or over regions of the zone(s).”; “Four optically read zones (each spanning four electrodes) are spaced apart from each other on the right side perimeter of the device.” (par [0053]).
As mapped with respect to claim 1, a larger region of Jebrail's electrode array encompassing the disclosed function-specific regions corresponds to the claimed functional zone. Within at least one such larger region:
a portion of one of Jebrail's heating zones corresponds to the first sub-zone;
one of Jebrail's magnetic regions corresponds to the second sub-zone;
one of Jebrail's optically read zones corresponds to the third sub-zone; and
another of Jebrail's four optically read zones corresponds to a fourth sub-zone, which is identical to the third sub-zone, because Jebrail expressly teaches four optically read zones, each spanning four electrodes, and performing the same optical-read function.
Jebrail additionally teaches that its drive electrodes form “a plurality of unit cells” and that “each cell or region of cells (multiple cells) may be controlled to perform a specified function,” supporting treatment of respective portions or collections of the electrode array as the mapped sub-zones and functional zones (par. [0085]).
Regarding claim 10, Jebrail further teaches one or more magnets arranged next to the first plate-like structure or the second plate-like structure (Par. [0082]). “the reaction mixture ... was exchanged between the Purification Module and Transfer conduit three times while engaging an external magnet beneath the interface area” (par [0082]); “the magnet may be positioned right under the heating zone when using resistive heating.” (par [0085]). The external magnet positioned beneath/right under the functional region of Jebrail’s DMF device corresponds to the claimed magnet arranged next to one of the plate-like structures.
Jebrail further teaches and configured to generate a magnetic field that penetrates the one or more droplets when they are located between the first and the second plate-like structure. “seven of the electrodes are configured as magnetic regions 605, which can apply a local (to that electrode) magnetic force to retain a magnetic bead or particle within a droplet on the electrode” (par [0053]); “One or more magnetic zones 603 may be used for turning on/off magnetic fields that may be useful to immobilize a magnetic particle” (par [0085]); “Some DMF apparatuses useful with the disclosure herein have a ‘two-plate’ format in which droplets are sandwiched between a top plate and a bottom plate.” (par [0076]).
Because Jebrail's magnetic field acts on magnetic particles within a droplet, the magnetic field necessarily penetrates the droplet, and Jebrail expressly places the droplets between the top and bottom plates. Accordingly, Jebrail teaches the entire first alternative of claim 10, and claim 10 is anticipated by Jebrail.
Regarding claim 11, Jebrail further teaches one or more output ports, each output port being configured to eject the one or more droplets from between the first plate-like structure and the second plate-like structure or from the fluid processing device (par. [0080]). “Some examples include withdrawing (a droplet) of fluid from a DMF apparatus; and drawing a (droplet of) fluid from a surface of digital microfluidic apparatus 320 through module interface 327 and into transfer conduit 313.” (par [0080]).
Jebrail further expressly teaches that the fluid application/extraction interface communicates with the space between the two plates through an opening (par [0021]). “a fluid application and extraction interface device configured to apply or remove fluid into the gap”; “wherein a distal end of the transfer conduit is coupled to an opening on one of: the first plate, the second plate or between the first and second plates.” (par [0021]). Thus, Jebrail's opening/module interface corresponds to the claimed output port, and the transfer conduit withdraws the droplet through that port from the space between the plate-like structures.
Jebrail additionally teaches this configuration in connection with its microfluidic channels (par. [0093]). “Fluid may be withdrawn from the air gap through the opening 1505 into the first channel 1501”; “fluid may be drawn from the air gap at or near the same opening 1505 into the second channel by applying negative pressure” (par [0093]).
Accordingly, Jebrail teaches the entire output-port alternative of claim 11, and claim 11 is anticipated by Jebrail. There is no need to separately establish the input-port alternative because claim 11 recites the two alternatives with “or.”
Regarding claim 18, Jebrail teaches a method of manipulating droplets (par [0006], Jebrail teaches that “The apparatus, devices, systems, and methods described herein generally involve manipulation of discrete samples of liquids (drops/droplets).” (par [0006]).
Jebrail teaches manipulating one or more droplets between a first plate-like structure and a second plate-like structure by electrowetting (Par. [0073]). Jebrail teaches that “fluid droplets are sandwiched in the purification module between a bottom plate and one or more top plates”; “Actuation electrodes on or adjacent to the bottom plate and counter electrodes on or adjacent to top plates work together to move fluid drops/droplets between the plates and/or along the top plate by applying voltage to adjacent positions to generate electrowetting forces.” (par [0073]).
Jebrail further teaches applying, by respectively operating sub-zones of a plurality of functional zones of the plate-like structures, at least two of heat, a magnetic field, and light to the one or more droplets. Jebrail teaches that “each cell or region of cells (multiple cells) may be controlled to perform a specified function,” that “The central heating zone(s) 609 may be used for heating a droplet,” and that “One or more magnetic zones 603 may be used for turning on/off magnetic fields that may be useful to immobilize a magnetic particle” (par [0085]).
As set forth with respect to claim 1, Jebrail's respective heating and magnetic regions correspond to the claimed sub-zones of the functional zones. Thus, operating the heating zone and magnetic zone applies at least two of heat and a magnetic field to droplets. Jebrail also demonstrates use of both functions during sample processing, including “40 min incubation at 35° C.” followed by engagement of “an external magnet beneath the interface area” to recover the bead-containing reaction mixture.
Regarding claim 19, Jebrail further teaches purifying, by one or more magnetic beads disposed within at least one of the sub-zones of the plurality of functional zones of the plate-like structures, the one or more droplets.
Jebrail expressly describes “extraction and purification of miRNA from human plasma” in its DMF system, wherein the plasma sample is mixed with “miRNA Binding Beads (80 µL)” and “the beads [are allowed] to bind miRNA in the Lysate” (par [0082]). Jebrail then teaches engaging an external magnet such that the beads are immobilized on the surface of the DMF device, removing the reaction mixture, reconstituting the beads with wash buffer, releasing the beads, and repeating the washing process.
Jebrail also expressly teaches the location of the magnetic particles in the mapped magnetic sub-zone: magnetic regions “can apply a local (to that electrode) magnetic force to retain a magnetic bead or particle within a droplet on the electrode.” (par [0053]). Jebrail further teaches that “magnetic particles holding an analyte of interest are magnetically held within the air gap ... while the fluid is exchanged between the reservoirs, enhancing binding and/or rinsing.” (par [0100]).
Thus, Jebrail's magnetic beads within the bead-containing droplet at the magnetic sub-zone perform the disclosed purification process.
Regarding claim 20, Jebrail further teaches wherein the one or more droplets comprise a sample of deoxyribonucleic acid (DNA).
Jebrail teaches that its methods generally involve “manipulation of discrete samples of liquids (drops/droplets)” and expressly teaches using those methods for “enriching for or purifying or partially purifying an analyte from a sample such as an RNA, DNA, protein,” as well as performing “DNA sequencing” (pars. [0006]-[0007]).
Thus, Jebrail expressly contemplates its manipulated liquid droplets containing DNA samples for processing.
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.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Jebrail et al. (US 2020/0061621) (Jebrail) in view of Zhou et al. (US 6,355,491) (Zhou).
Regarding claim 3, Jebrail does not expressly teach that wherein in the second sub-zone, a metal coil is embedded in the first plate-like structure or in the second plate-like structure, the metal coil being configured to generate a magnetic field, as recited by claim 3.
Zhou teaches an electromagnetic chip having micro-electromagnetic units formed on a substrate, wherein magnetic fields are generated by conductive loops (col. 10, ll. 28-35, “each electromagnetic unit comprises a magnetic core on the substrate, single or multiple turns of electric conductive traces about the magnetic core, means for applying electric current to the conductive traces from an electric current source”). Zhou further teaches that the conductive traces forming the electromagnetic units may be metal, including “aluminum, gold, silver, tin, copper, platinum, palladium,” and may comprise multiple turns fabricated using multilayer microfabrication (col. 10, ll. 1-13).
Zhou further teaches forming the conductive traces specifically as micro-coils within a multilayer chip structure (col. 13, ll. 15-37, “The magnetic strength of the selected unit can be increased further by using microfabrication methods to actually produce micro-coils surrounding each core.”; “The micro-coils are fabricated from conductive traces as mentioned above. Again, conductive layers of doped silicon and metal (e.g., aluminum) are used alternatingly.”). Zhou teaches that the micro-coil traces are successively formed and covered by insulating layers, thereby integrating the micro-coils into the multilayer substrate structure (col. 13, ll. 38-65; col. 14, ll. 1-23).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify Jebrail's magnetic sub-zones by incorporating Zhou's metal micro-coils into the plate/substrate underlying the respective magnetic sub-zones, motivated to provide localized magnetic-field generation in an integrated microfabricated structure and to increase the magnetic-field strength at the selected magnetic sub-zone, as Zhou teaches that micro-coils surrounding the selected unit increase its magnetic-field strength (Zhou, col. 13, ll. 15-29). The resulting device would have in the second sub-zone, a metal coil embedded in the first plate-like structure or in the second plate-like structure, the metal coil being configured to generate a magnetic field, as recited by claim 3.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Jebrail et al. (US 2020/0061621) (Jebrail) in view of Zhang et al. (US 2022/0266245) (Zhang).
Regarding claim 4, Jebrail does not expressly teach wherein in the second sub-zone, a permanent magnet is embedded in the first plate-like structure or in the second plate-like structure, the permanent magnet being configured to generate a magnetic field.
Zhang teaches a permanent magnet embedded in a substantially flat supporting member and configured to generate a magnetic field. Zhang teaches that “In another example, the magnet may be embedded in the substantially flat surface of the base member. A hole/space may be provided in the base member for accommodating the magnet such that the magnet does not protrude from the substantially flat surface.” (par [0049]); “the magnet functions to manipulate e.g. immobilise a droplet which is doped with magnetic particles by applying a magnetic field which exerts a magnetic force on the magnetic particles.” (par [0050]); “the magnet may be a permanent magnet or an electromagnet. For example, the magnet may be a permanent magnet e.g. rounded bar permanent magnet which can be embedded in the hole/space provided in the base member.” (par [0051]).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify Jebrail's magnetic sub-zone by embedding Zhang's permanent magnet in the plate-like structure at the magnetic sub-zone, motivated to provide the magnetic field while maintaining a substantially flat surface, because Zhang teaches accommodating the magnet in a hole/space so that the magnet does not protrude from the substantially flat surface (Zhang, par. [0049]). The resulting device would have wherein in the second sub-zone, a permanent magnet is embedded in the first plate-like structure or in the second plate-like structure, the permanent magnet being configured to generate a magnetic field, as recited by claim 4.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Jebrail et al. (US 2020/0061621) (Jebrail) in view of Sears et al. (US 2016/0262454) (Sears).
Regarding claim 5, Jebrail does not expressly teach wherein in the first sub-zone, a micro-heater is embedded in the first plate-like structure or in the second plate-like structure, as recited by claim 5.
Sears teaches a microfluidic device having a substantially chip-shaped substrate with an embedded heater. Sears teaches that “the microfluidic vaporizer 330 comprises a substrate 345 that is substantially chip shaped”; “In some embodiments, the heater 355 may be embedded in the substrate 345, such as being positioned within a well or other indentation in the substrate.” (par [0072]). Sears further expressly teaches that the embedded heater may be a microheater (par. [0073], “In some embodiments, the heater 355 may be characterized as a microheater. In particular, the microheater can be characterized as a Micro-Electro-Mechanical Systems (MEMS) based heater.” (par [0073]).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify Jebrail's heating sub-zone by embedding Sears's microheater in the plate-like structure at the heating sub-zone, motivated to improve heating response time while reducing power consumption, because Sears teaches that MEMS-based microheaters provide “low power input requirement and very short response time” and provide rapid heating in a microfluidic device (Sears, Par. [0073]). The resulting device would have wherein in the first sub-zone, a micro-heater is embedded in the first plate-like structure or in the second plate-like structure, as recited by claim 5.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Jebrail et al. (US 2020/0061621) (Jebrail) in view of Chediak et al. (US 2005/0157301) (Chediak).
Regarding claim 7, Jebrail does not expressly teach wherein in the third sub-zone, a light emitting device and a photodetector are respectively embedded in the first plate-like structure or in the second plate-like structure, as recited by claim 7.
Chediak teaches integrating a light emitting device and photodetector with a microfluidic substrate (par. [0072]). Chediak teaches that “we describe the heterogeneous integration into a microanalytical system of a CdS filter, an (In, Ga)N blue LED, a Si PIN photodetector and disposable poly(dimethylsiloxane) (PDMS) microfluidic channels.” (par [0072]). Chediak further teaches that light emitted by the LED is directed to the sample and the emitted light returns to the photodetector (par. [0073], “FIG. 7 depicts in schematic cross-sectional view, the path of the exciting light from the LED to the sample, and the return path of the emitted light to the p-i-n (or PIN) photodetector.” (par [0073])
Chediak further teaches an integrated substrate configuration in which the optical components are incorporated into the substrate structure supporting the microfluidic channel. Chediak teaches that “Another approach to an integrated microanalytical system and its fabrication relates to the vertical integration of excitation, filtering and photodetection in a stack approximately 10 μm thick. This stack is integrated with a microfluidic channel structure” (par [0090]); “a microchannel is typically formed in a silicon substrate” (par [0091]), “The polyimide layer or seal typically covers substantially all component-containing areas of the substrate.” (par [0092])
Chediak specifically teaches incorporating the light emitting device into that silicon substrate. “A LED, typically (In,Ga)N, or other light source, is bonded to the silicon substrate that has been prepared by the preceding steps.” (par [0093]), and incorporating the photodetector into the same substrate stack, “A transparent conductor is deposited onto the insulting buffer layer to serve as a ground contact for both the LED and the photodetector” (par [0096]); “N-type CdS is deposited onto the ITO followed by the deposition of p-type CdTe. The CdS/CdTe form a p-n photodetector.” (par [0097]). Thus, Chediak's LED and photodetector integrated into the substrate stack correspond to the claimed light emitting device and photodetector embedded in a plate-like structure.
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify Jebrail's imaging/optical sub-zones by incorporating Chediak's integrated LED and photodetector into the plate-like substrate at the optical sub-zone, motivated to make the optical detection system more compact and portable, because Chediak teaches that its integrated microsystems are “less expensive and more compact” and that components may be combined on a single substrate (Chediak, Par. [0014]). The resulting device would have wherein in the third sub-zone, a light emitting device and a photodetector are respectively embedded in the first plate-like structure or in the second plate-like structure, as recited by claim 7.
Claim 8 and 12-17 are rejected under 35 U.S.C. 103 as being unpatentable over Jebrail et al. (US 2020/0061621) (Jebrail) in view of Umapathi (US 2020/0114360) (Umapathi).
Regarding claim 8, Jebrail teaches an optically transparent portion of the plate structure at an optical readout region. Jebrail teaches that “Any of the cartridges described herein may also include one or more transparent window regions 711 for optically imaging one or more regions (readout regions) within the air gap.” (par [0090]). Thus, Jebrail teaches wherein in the third sub-zone, the first plate-like structure or the second plate-like structure is transparent to light of at least one predetermined wavelength, because transparent window region 711 permits light used for optical imaging to pass through the plate structure into or from the readout region.
Jebrail does not expressly teach a light emitting device, which is configured to emit the light of the at least one predetermined wavelength, and a photodetector are respectively arranged on or besides an outer surface of the first plate-like structure or of the second plate-like structure, as recited by claim 8.
Umapathi teaches a light emitting device, which is configured to emit the light of the at least one predetermined wavelength (par. [0208]). Umapathi teaches that “A light source 1152 (broad spectrum light, single frequency, or other) may be passed through optics 1154 to condition the light (filters, diffraction gratings, mirrors, etc.) and then illuminate a sample 1156 sitting on an electrowetting device.” (par [0208]). A single-frequency light source corresponds to a light emitting device configured to emit light of a predetermined wavelength.
Umapathi further teaches and a photodetector are respectively arranged on or besides an outer surface of the first plate-like structure or of the second plate-like structure (par. [0208]), “An optical detector on the other side of the electrowetting device is configured to detect the spectrum of light passing through the sample for analysis.” (par [0208]); “sample 1156 may be sandwiched between two plates 100, 1160. In some cases the electrowetting chip and the electrodes may be transparent. In some cases, there may be a hole in the electrode on which the sample is located, to allow passing of light from the source through the sample to the optical detector.” (par [0209]). The light source and optical detector positioned on opposite sides of Umapathi's two-plate electrowetting device correspond to the claimed light emitting device and photodetector respectively arranged on or beside outer surfaces of the plate-like structures.
It would have been obvious to one of ordinary skill in the art before the effective filing date to provide Jebrail's optically read sub-zone with Umapathi's light source and photodetector arranged on opposite sides of the plate structures, motivated to improve the optical analysis capability of Jebrail's optically read zones by enabling illumination and optical detection of samples, because Umapathi teaches that its optical inspection arrangement may be used for “measuring concentration of nucleic acids, measuring quality of nucleic acids, measuring density of cells, measuring extent of mixing between two liquids, measuring volume of sample, measuring fluorescence of sample, measuring absorbance of sample, quantification of proteins, colorimetric assays and other biological assays” (Umapathi, par. [0208]).
The resulting device would have wherein in the third sub-zone: the first plate-like structure or the second plate-like structure is transparent to light of at least one predetermined wavelength; and a light emitting device, which is configured to emit the light of the at least one predetermined wavelength, and a photodetector are respectively arranged on or besides an outer surface of the first plate-like structure or of the second plate-like structure, as recited by claim 8.
Regarding claim 12, Jebrail teaches a fluid processing device according to claim 1 as set forth above.
Jebrail does not expressly teach a fluid processing array comprising a plurality of fluid processing devices according to claim 1, as recited by claim 12. Applicant's specification confirms that claim 12 is directed to an array containing multiple fluid-processing devices, rather than merely the plurality of electrodes within a single device.
Umapathi teaches arranging multiple electrowetting processing structures for parallel operation. In particular, Umapathi teaches that “an electrowetting device may incorporate one or more mixing stations 1120” and that “[o]n the left is a 2x2 collection of electrowetting-based mixing stations that may be operated in parallel” (par. [0197]). Umapathi further teaches that a parallel station may contain “any number of individual mixers in an MxN pattern” (par. [0198]).
Umapathi also expressly applies this parallel architecture to multifunctional electrowetting processing stations. Umapathi teaches that a magnetic bead station “may be configured to mix samples and reagents, apply heating or other processes,” and that “each magnetic bead station may have the ability to locally turn on and turn off a strong and varying magnetic field” (par. [0203]). Umapathi then expressly states that “Multiple magnetic bead stations may be configured to be operated in parallel, as described above for parallel mixing stations” (par. [0204]).
It would have been obvious to one of ordinary skill in the art before the effective filing date to provide a plurality of Jebrail's fluid processing devices in an array, as taught by Umapathi's parallel arrangement of multiple electrowetting processing stations, motivated to increase parallel sample processing capability and throughput, because Umapathi expressly teaches operating multiple electrowetting processing stations in parallel (pars. [0197], [0198], [0204]). The resulting arrangement would constitute a fluid processing array comprising a plurality of fluid processing devices according to claim 1, as recited by claim 12.
Regarding claim 13, the combination of Jebrail and Umapathi further teaches wherein the fluid processing array is a chip or a panel. Claim 13 requires only this first alternative or the alternative involving a plurality of chips.
Umapathi teaches that the electrode array itself may be implemented as a digital microfluidic chip (par. [0184]). “The lid may have a clear window 1102 to view the motion of droplets on the electrode array, which may be formed as a digital microfluidic chip. The box may house a digital microfluidic chip 100 capable of moving, merging, splitting droplets, in which the droplets carry biological reagents.” (par [0184]).
Umapathi further teaches that this electrowetting architecture contains a plurality of processing stations arranged for parallel operation (par [0197]). Umapathi teaches that “an electrowetting device may incorporate one or more mixing stations 1120. On the left is a 2x2 collection of electrowetting-based mixing stations that may be operated in parallel.” (par [0197]). Umapathi also teaches that a parallel station “may also have any number of individual mixers in an MxN pattern 1122” (par [0198]).
Thus, in the Jebrail-Umapathi combination discussed for claim 12, the plurality of fluid-processing devices is arranged as an electrode array implemented on a digital microfluidic chip, thereby teaching the fluid processing array is a chip, as recited by claim 13.
Regarding claim 14, the combination further teaches wherein the fluid processing array further comprises one or more control units configured to address and control individually each sub-zone of each functional zone in each fluid processing device in the fluid processing array.
Jebrail teaches individual control of the cells or regions that correspond to the claimed sub-zones (par. [0085]). “The drive electrodes under the secured dielectric may therefore form a plurality of unit cells (one drive electrode per unit cell), and each cell or region of cells (multiple cells) may be controlled to perform a specified function.” (par [0085]). Jebrail then identifies those functions as including cooling/heating and magnetic-field functions, and also identifies imaging/optical zones. Thus, under the mapping used for claim 1, each Jebrail cell or region of cells corresponding to a respective heat, magnetic, or optical sub-zone is individually controllable to perform its specified function.
Umapathi teaches one or more control units configured to address and control individually the functional portions of an electrowetting array. Umapathi teaches that the wetting affinity of the surface “can be individually varied in a controlled manner by application of voltage to respective electrode pads” and that “A control is designed to alter the wetting characteristic of varying-wettability portions of the surface over respective electrode pads to effect induced motion of the droplets over the tracks.” Umapathi further expressly teaches “a controller operatively coupled to said first plurality of electrodes and said second plurality of electrodes,” wherein the controller directs subsets of the electrodes to supply the electric field (claims 1 and 9).
Umapathi also teaches independent control of functional processing stations, stating that “the individualized heating elements may permit each station to be controlled to a separate temperature” (par [0200]).
It would have been obvious to one of ordinary skill in the art to provide the Jebrail-Umapathi fluid-processing array of claim 12 with Umapathi's controller for individually addressing and controlling the respective functional cells/regions, motivated to permit independent operation of the respective processing regions and parallel processing stations, because Umapathi teaches individually controlling electrode portions and separately controlling individual processing stations. The resulting array would comprise one or more control units configured to address and control individually each sub-zone of each functional zone in each fluid processing device in the fluid processing array, as recited by claim 14.
Regarding claim 15, Jebrail teaches a fluid processing system comprising at least one fluid processing device according to claim 1, as set forth above with respect to claim 1.
Jebrail further teaches individually controllable functional regions (par [0085]). “The drive electrodes under the secured dielectric may therefore form a plurality of unit cells (one drive electrode per unit cell), and each cell or region of cells (multiple cells) may be controlled to perform a specified function.” (par [0085]). Jebrail identifies the specified functions as including heating a droplet, applying magnetic fields, and imaging/optical functions.
Jebrail does not expressly teach a control unit configured to address and control individually each sub-zone of each functional zone in the fluid processing system, as recited by claim 15.
Umapathi teaches such individual control of an electrowetting electrode array (par [0003]). “A set of electrode pads is arranged in an array or in paths defining one or more tracks over which liquid droplets may be induced to move over a sequence of the electrode pads”; “A control is designed to alter the wetting characteristic of portions of the surface over respective electrode pads to effect induced motion of the droplets over the tracks, the wetting characteristic to be altered by controlling charging and discharging of the electrode pads in a desired sequence.” (par [0003]). Umapathi further teaches that feedback from sensors may be provided to “computers that control the electrical flow to the electrodes, so that the droplets may be accurately controlled to achieve high throughput rates with accurate drop positioning, mixing, etc.” (par [0191]).
It would have been obvious to provide Jebrail's individually controllable functional cells/regions with Umapathi's control unit for individually addressing and controlling the respective electrode regions, motivated to improve accurate droplet positioning and increase processing throughput, as taught by Umapathi (Par. [0191]). The resulting system would comprise a control unit configured to address and control individually each sub-zone of each functional zone in the fluid processing system, as recited by claim 15.
Regarding claim 16, the combination further teaches wherein the control unit is configured to control an operation of one or more sub-zones of any functional zone of the fluid processing device or of a fluid processing array, so as to apply heat, a magnetic field or light, in any order, to one or more droplets.
Jebrail teaches that “each cell or region of cells (multiple cells) may be controlled to perform a specified function” and that “The central heating zone(s) 609 may be used for heating a droplet” (par [0085]).
Umapathi similarly teaches that an electrowetting chip may include incubation stations having independently controllable heating functionality (par [0200]). “Each individual incubator 1128 may integrate one or more functions to be applied to liquid samples such as mixing, heating”; “the individualized heating elements may permit each station to be controlled to a separate temperature” (par [0200]).
Umapathi further teaches magnetic functionality within another processing station (par [0203], “The station may be configured to mix samples and reagents, apply heating or other processes, in sequential order”; “each magnetic bead station may have the ability to locally turn on and turn off a strong and varying magnetic field”). Umapathi also teaches optical stations having a light source that illuminates a sample and an optical detector that detects the resulting light (par [0208]).
Thus, the combination teaches individually controllable sub-zones capable of applying heat, a magnetic field, or light to droplets. Further, because Umapathi teaches programmable processors executing instructions to perform the disclosed processes (par [0233]) and processing operations performed sequentially (par [0203]), it would have been obvious to program the control unit to operate the respective independently controllable functional zones in an order appropriate for the particular assay or workflow.
Accordingly, the combination teaches the first alternative of claim 16. There is no need to separately establish the simultaneous-operation alternative because claim 16 recites the alternatives with “or.”
Regarding claim 17, the combination further teaches wherein the control unit is further configured to control a movement of one or more droplets to one or more functional zones of the fluid processing device or of the fluid processing array.
Umapathi expressly teaches controller-based movement of droplets to selected locations on the electrowetting electrode array (par [0179]). “When voltage is removed from electrode 120i and applied to another adjacent electrode 120j, the surface returns to original hydrophobic state and the droplet is pushed out”; “By sequentially controlling the voltage applied to an electrode grid, a droplet's position on a surface may be precisely controlled.” (par [0179]).
Umapathi further teaches that the electrowetting chip has “one or more stations for various functions” (par [0195]) and specifically teaches movement of droplets to a functional processing station (par [0197]), “droplets of two reagents may be brought together at a mixing station, and then mixed by running the merged droplet around the outer eight electrodes of the 3x3 grid, or running through other patterns designed to mix the two original droplets.” (par [0197]).
Thus, Umapathi's controller sequentially controls the electrode grid to move droplets to selected functional processing stations, corresponding to control a movement of one or more droplets to one or more functional zones of the fluid processing device or of the fluid processing array.
Accordingly, the combination teaches the first alternative of claim 17. The second alternative—movement between separate fluid-processing devices—does not need to be established because claim 17 uses “or.”
Conclusion
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/XIAOYUN R XU, Ph.D./ Primary Examiner, Art Unit 1797
