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 .
DETAILED ACTION
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office Action.
Status of Claims
Claims 1-7 and 9-23 are currently pending. Claims 1 and 7 have been amended by Applicants’ amendment filed 06-18-2026. Claim 8 has been canceled by Applicants’ amendment filed 06-18-2026. No claims have been added by Applicants’ amendment filed 06-18-2026.
Applicant's election without traverse of Group I, claims 1-8, directed to a cell preparation system, in the reply filed November 6, 2024 was previously acknowledged.
Claims 9-23 were previously withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.
The restriction requirement was deemed proper and was made FINAL.
The claims will be examined insofar as they read on the elected species.
A complete reply to the final rejection must include cancellation of nonelected claims or other appropriate action (37 CFR 1.144) See MPEP § 821.01.
Therefore, claims 1-7 are under consideration to which the following grounds of rejection are applicable.
Priority
The instant application filed June 6, 2022 is a 371 of PCT/US2020/025044, filed March 26, 2020.
Withdrawn Objections/Rejections
Applicants’ amendment and arguments filed June 18, 2026 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Any rejection and/or objection not specifically addressed below are herein withdrawn.
Double Patenting
The provisional rejection of claims 1-8 is withdrawn on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 8, 10, 12, 14, 16, 17, 19-22, 25, 28-31 and 34 of copending US Patent Application No. 18/564,484 in view of Koltay because the claims are patentable distinct.
In view of the withdrawn rejection, Applicant’s arguments are rendered moot.
Claim Rejections - 35 USC § 103
The rejection of claims 1-8 is withdrawn under 35 U.S.C. 103 as being unpatentable over Koltay et. al. (hereinafter “Koltay”) (US Patent No. 8834793, issued September 16, 2014; of record) in view of Sharei et al. (hereinafter “Sharei”) (US Patent No. 1069644, issued June 30, 2020; WO2013059343, filed October 17, 2012; of record) as evidenced by Renaud et al. (hereinafter “Renaud”) (US Patent Application Publication 20080286751, published November 20, 2008).
The combined references of Koltay and Sharei do not specifically exemplify a filter device configured to gate a subset of electrical signals as recited in claim 1.
In view of the withdrawn rejection, Applicant’s arguments are rendered moot.
(2) Claims 1-8 are rejected under 35 U.S.C. 103 as being unpatentable over Cho et al. (hereinafter “Cho”) (US Patent No. 10816550, issued October 27, 2020; previously published as WO2014062719, published April 24, 2014) in view of Sharei et al. (hereinafter “Sharei”) (US Patent No. 1069644, issued June 30, 2020; WO2013059343, filed October 17, 2012; of record).
The combined references of Cho and Sharei do not specifically exemplify a filter device configured to gate a subset of electrical signals as recited in claim 1.
In view of the withdrawn rejection, Applicant’s arguments are rendered moot.
Maintained Objections/Rejections
Claim Interpretation: The constriction as recited in claim 1 is interpreted to refer to any constriction that deforms a cell traveling through the fluidic channel including a fluidic channel having a diameter/width that is smaller than the diameter/width of a cell.
The term “configured to measure a state within the constriction” as recited in claim 1 is interpreted to refer to a sensor capable of measuring any type of state within the constriction, such as: the number of cells, flow rate, fluorescence, channel pressure, temperature, etc.
The terms “a fluidic channel configured to” such as recited in claim 1 is interpreted to mean that the fluidic channel is configured to both receive a plurality of cells and to transport a plurality of cells.
Claim Rejections – 35 USC § 112(b)
The rejection of claims 1-7 is maintained under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards
as the invention.
Claim 1 is indefinite for the recitation of the term “the respective detection device” such as recited in claim 1, lines 19-20. There is insufficient antecedent basis for the term “the respective detection device” in the claim because claim 1, lines 4-5 and 18 recite the terms “a plurality of detection devices” and “detection device.” The Examiner suggests that Applicant amend the claim to recite, for example, “from the signal generator to each detection device of the plurality of detection devices.”
Claim 1 is indefinite for the recitation of the term “the electric field” such as recited in claim 1, lines 20 and 21. There is insufficient antecedent basis for the term “the electric field” in the claim because claim 1, line 13 recites the term “an electrical field.” The Examiner suggests that Applicant amend the claim to recite, for example, “applying an electric field to a cell.”
Claims 1 and 7 are indefinite for the recitation of the terms “different” and “varies” such as recited in claim 1, line 21 because the terms “different” and “varies” are relative terms that render the claims indefinite. The terms “different” and “varies” are not defined by the claims, and the Specification does not provide a standard for ascertaining the requisite amount of ‘difference’ or ‘variation’ as compared to some other value that qualifies as a difference in the electric field or a variation in the shape of a constriction, such that one of ordinary skill in the art would not be reasonably appraised of the scope of the invention.
Claim 7 is indefinite for the recitation of the term “wherein each of the plurality of detection devices comprises a different constriction” such as recited in claim 7, lines 1-2 because claim 7 depends from instant claim 1, wherein claim 1 already recites what the plurality of detection devices comprise (e.g., a constriction, a pair of electrodes, a sensor, etc.), such that dependent claim 7 cannot recite that the plurality of detection devices comprises something different (e.g., a constriction having a shape) and, thus, the metes and bounds of the claim cannot be determined. The Examiner suggests that Applicant amend the claim to recite, for example, “wherein the constriction comprise a shape” or “wherein each of the plurality of detection devices further comprises.”
Claim 7 is indefinite for the recitation of the term “a different constriction” such as recited in claim 7, line 2. There is insufficient antecedent basis for the term “a different constriction” in the claim because claim 1, line 11 recites the terms “a constriction.”
Claims 2-6 are indefinite insofar as they ultimately depend from instant claim 1.
Claim Rejections - 35 USC § 112(d)
The rejection of claim 7 is maintained under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 7 recites (in part): “wherein each of the plurality of detection devices…varies between the plurality of detection devices” in lines 1-4 because claim 7 depends from instant claim 1, where claim 1 already recites what each of the plurality of detection devices comprises, while dependent claim 7 recites that each of the plurality of detection devices instead comprises a different constriction. Thus, claim 7 is an improper dependent claim for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
New Objections/Rejections
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 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.
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 1-7 are rejected under 35 U.S.C. 103 as being unpatentable over Zahn et al. (hereinafter “Zahn”) (US Patent No. 10927333, issued December 14, 2021; also WO2017040995, filed September 16, 2016) in view of Shkolnikov et. al. (hereinafter “Shkolnikov”) (US Patent No. 11198841, issued December 14, 2021; also WO2018226240, published August 8, 2018); and further in view of Sano et al. (hereinafter “Sano”) (Analytical Chemistry, 2019, 91, 12890-12899). This is a new matter rejection. This is a new rejection necessitated by amendment of the claims in the response filed 06-18-2026.
Regarding claims 1 and 7, Zahn teaches systems and methods for cell electroporation and molecular delivery using an intelligent, feedback controlled, microscale electroporation system for transfecting single cells (Abstract). Zahn teaches a system for electroporating a biological cell, the system comprising: a microfluidic channel adapted to receive a flow of a plurality of biological cells in a buffer solution, wherein the microfluidic channel comprises a detection area; a pair of electrodes adapted to apply an electrical field across the detection area; a signal generator unit capable of generating a cell detection signal and a permeabilization signal through the electrodes; a sensing unit adapted to detect the impedance of the detection area; and a controller unit adapted to control the signal generator unit according to the impedance detected by the sensing unit (interpreted as a system comprising a channel; detection area; a pair of electrodes to apply an electrical field; signal generator; sensor to measure impedance; and a controller, claim 1) (col 2, lines 7-20). Zahn teaches that the microchannel is drained, and excess BSA solution was removed from the outlet reservoir (interpreting the outlet reservoir as a waste receptacle; and component for removing solution as the system comprising an ejector, claim 1) (col 20, lines 30-32). Zahn teaches that the microfluidic channel is capable of hydrodynamically centering the flow of a plurality of biological cells through the detection area, wherein the system further comprises a second microfluidic channel adapted to receive a flow of buffer, and wherein the second microfluidic channel comprises a second detection area, wherein the sensing unit is adapted to detect the impedance of the second detection area (interpreting the hydrodynamic centering as configured for single file transport of cells; multiple detection areas; and a plurality of detection devices, claim 1) (col 2, lines 38-45). Zhan teaches that the 3-inlet approach hydrodynamically focuses the cells to ensure that the cells enter the center of the operating region of the device in single file (interpreting the hydrodynamic focusing as an ejector configured to eject the cells into the waste receptacle and well plate, claim 1) (col 12, lines 16-19). Zhan teaches that fabrication includes PDMS and sputtered glass slide treated with oxygen plasma to activate the surfaces and bonded together with feature alignment, where the microchannel can be 1 cm long, 150 mm wide, and 10 mm deep; and that traces for the electrodes were patterned lithographically on glass substrates and recesses were etched with 10:1 buffered hydrofluoric acid for 1 minute to a depth of -2000 A (interpreting the system to comprise as a well plate, claim 1) (col 11, lines 18-21). Zahn teaches that a pair of microelectrodes with a spacing of 120-400 μm is defined at a designated location along each microchannel, such that the inlets are connected to a syringe pump using polyethylene tubing for cell and sample introduction (interpreted as a pair of electrodes that also act as sensors and detection device for multiple microchannels/multiple detection devices, claim 1) (col 11, lines 21-26). Zahn teaches that electrical measurements for cell detection can also be verified with optical visualization of cells (not shown) via a visualization system integrated with the smart electroporator (interpreted as optical detectors, claim 1) (col 14, line 67; and col 15, lines 1-3). Zahn teaches in Figure 3C, in an embodiment, the system can also include a second, identical microchannel 350 with electrodes. Zahn teaches that the second, identical microchannel can be flowing with a buffer solution but no cells, and the impedance value of the second, identical microchannel can be sampled in parallel to the first microchannel through which cells are flowing to provide an ideal reference signal for differentiation and aid in detecting fast-moving, single cells, such that the microelectrodes from each of the two microchannels can each be connected to a current-to-voltage converter 318(a) and 318(b), which are in turn connected to a lock-in amplifier 325; and the system can include an imaging device such as a fluorescent imaging device capable of imaging the permeabilization stage and the delivery stage of the smart electroporation system (interpreting the two channels connected to a converter and imaging device as comprising a plurality of constrictions and detection devices, claim 1) (col 11, lines 30-45; and Figure 3C). Zhan teaches in Figure 3D that a microchannel design that consists of a gradually narrowed constriction can be employed, wherein the design serves to increase the cell volume fraction, detection signal to noise ratio, as well as amplify the applied electric field due to concentration of the electric field through the constriction, such that the length of the microchannel constriction provides the means to increase cell transit time in the detection area, which serves to allow longer time for characterizing detailed electrical information from the cell membrane before, during and after reversible or irreversible electroporation such that, for example, wherein the width of the constriction is tailored according to the cell size to provide a good fit that allows high electrolyte current displacement and smooth, continuous passage of the single cells through the constriction channel (interpreting the channel including a gradually narrowed constriction as a plurality of constrictions of varying widths, claims 1 and 7) (col 14, lines 15-33; and Figure 3D). Figure 3D (in part) is shown below:
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Zahn teaches that Figure 5B shows an automatic real-time single cell detection and triggered signal tracking plot illustrating changes in impedance upon detection of each cell in a continuous flow, such that in the illustrated current-time plot, with the passing of each single cell through the detection area (constriction length), a high 37 dB signal-to-noise ratio was obtained, and each dip 501(n) provides information on the duration, velocity, and impedance magnitude on the cell (interpreted as a plurality of sensors/detector devices configured to measure a state of the cell, claim 1) (col 15, lines 4-11; and Figure 5B). Zahn teaches that Figure 4, step 404, shows changes in the cell impedance can be detected by continually monitoring the impedance using a sensing unit, wherein the sensing unit comprises a lock-in amplifier, such that a frequency lock-in amplification technique can be implemented to distinguish cell specific signals, where the lock-in amplifier acts as a band-pass filter around a reference signal frequency, such that the noise can be removed by performing a Fourier transform on the input signal at the frequency and phase carried by the reference signal (interpreting the lock-in amplifier and bandpass filter as a filter device configured to gate a subset of electrical signals, claim 1) (col 15, lines 13-21; and Figure 4). Zahn teaches that a low-pass filter rejects everything but the DC component, wherein the signal is separately multiplied by independent reference sine and cosine waves to extract the phase information required to calculate the amplitude of the final signal; and that to determine the optimal sensing frequency for the lock-in amplifier, an impedance analyzer can be used (interpreting the low pass filter as a filter that gates a subset of electrical signals, claim 1) (col 15, lines 29-34). Zahn teaches that Figure 8A illustrates automatic real-time single cell detection and triggered pulse tracking plot showing that the above system and method detects and electroporates each passing single cell with a high accuracy (col 17, lines 14-17; and Figure 8A). Zhan teaches that five electric fields (0.44, 0.58, 0.70, 0.87, 1.05 kV/cm, as measured at the cell) were investigated at five pulse durations each (0.2, 0.8, 1.0, 3.0, 5.0 ms) to impose different degrees of cell-membrane permeabilization (interpreted as variations in the electrical field, claim 1) (col 20, lines 47-51).
Regarding claims 2 and 3, Zahn teaches that the thresholds described above can be selected from a database, comprising a data set of calibration results performed beforehand, and/or derived real time using computational models, based on the cell size and type of cell population of the detected cell (interpreted as cell size, type of cell, claim 2) (col 6, lines 58-63). Zahn teaches that the controller unit can utilize the impedance readings from the lock-in amplifier 325 and the signal characteristics from the signal generator unit 326 to generate the control signal, such that the signal generator unit can be used to generate signals and/or communicate with the electrodes via the feedback loop (interpreted as comprising a controller, claim 2) (col 10, lines 24-29). Zahn teaches that the sensing unit monitors the change in impedance of the cell as its membrane becomes more conducting due to the permeabilization of its membrane as a result of the permeabilizing DC plus waveform, wherein once permeabilized 220, the cell becomes conductive, and the impedance drops 204 (and the electric current increases) (interpreted as the controller configured to determine conductivity, claim 2) (col 7, lines 2-5; and col 9, lines 35-37).
Regarding claim 4, Zahn teaches that in step 402, a first cell detection signal is applied across the detection area and the impedance is monitored, wherein the first cell detection signal can be an AC detection waveform obtained either from simulation models or known literature, such that the AC detection waveform can be used to monitor the presence or absence of a cell within the detection area; and in step 403, a second permeabilization signal is applied across the detection area when a biological cell is detected by an increased impedance value over a baseline threshold (interpreted as measuring impedance, claim 4) (col 12, lines 35-44).
Regarding claim 5, Figure 2A shows the electrode sensors within the channel (interpreted as sensors disposed within the constriction of the detection device, claim 5) (Figure 2A). Zahn teaches in Figure 3B, the microfluidic channels 313 can be patterned on the glass slides using techniques such as lithography, and may be configured for hydrodynamically focusing (using a fluid microchannel 315) a single cell 316 for delivery between the electrodes (interpreted as sensors disposed within the constriction of the detection device, claim 5) (col 10, lines 57-62). Figure 2A (in part) is shown below:
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Regarding claim 6, Zahn teaches that the depth of the channel can be defined at 10 µm depth to limit the solution volume at the constriction region which is also the detection and pulsing region, wherein planar electrodes can be placed outside of the channel constriction in order for the amplification of the applied electric field (interpreted as sensors disposed outside the constriction, claim 6) (col 14, lines 38-43).
Regarding claim 7, Zhan teaches that the permeabilization apparatus 320 can include a DUT 328 a closed microfluidic channel of various designs that permits single cell flow through a confined space to allow recognizable or enhanced cell overall impedance or membrane permeabilization signal (interpreting a DUT to describe different constrictions having different shapes, claim 7) (col 10, lines 32-36).
Zahn does not specifically exemplify constrictions having an additional type of ejector (claim 1, in part); or a channel having additional constriction shapes (claim 7, in part).
Regarding claim 1 (in part), Shkolnikov teaches a microfluidic device can include a microfluidic channel including an electrode placed at opposite ends of the microfluidic channel to create an electrical field within the channel and an ejection device to eject at least one cell porated within the electrical field, wherein a cassette can include a substrate, a die coupled to the substrate, a microfluidic channel defined within the die, the microfluidic channel including a necked portion to receive a cell therein and at least two electrodes each placed at a first and a second end of the microfluidic channel to apply an electric field to the cell above a proration threshold and a cell ejection device to eject the cell from the die (interpreted as comprising an ejector, claim 1) (Abstract). Shkolnikov teaches that the microfluidic channel (105) can include a narrowed portion placed between the electrodes (110), wherein the microfluidic channel (105) allows a number of cells to pass therethrough and may be forced to pass through the narrowed portion of the microfluidic channel (105), such that this can cause the cells to pass through the narrow portion at a cell by cell basis or at least in a single file manner (interpreted as a constriction) (col 3, lines 6-13). Shkolnikov teaches that these electrical traces can be selectively electrically coupled to an electrical dispensing device that van carry the microfluidic device (100) over a well plate to dispense at least one cell from the microfluidic device (100), wherein the electrical dispensing device can be the source of the voltage used by the microfluidic device (100) to, at least, create the electrical field in the narrow portion of the microfluidic channel (105) (interpreted as an ejector configured to dispense into a well plate, claim 1) (col 4, lines 4-11). Shkolnikov teaches that the ejection device (115) can include a detector that detects the presence of at least one cell within a firing chamber housing the ejection device (115), which can include a detector that detects the type of cell within the firing chamber, such that these detectors can be used to allow the microfluidic device (100) to eject a single cell from the microfluidic device (100) and into an individual well of a well plate, such that this allows for the porated cells to be individually ejected into wells defined within a well plate or into a disposal location such as a spittoon (interpreted as injecting into a well plate or waste receptacle, claim 1) (col 4, lines 24-34). Shkolnikov teaches that the various microfluidic channels (215) defined in the die (210) of the cassette (200) can include any number of additional sensors used to detect the presence of a cell or a type of cell, such that the cassette (200) can be controlled by an electrical dispensing device to eject a cell or certain type of cell from the die (210) following the poration process accomplished by the electrodes (interpreted as each constriction comprising a detection device, claim 1) (col 6, lines 5-11). Shkolnikov teaches that a number of traces (435) can electrically couple each of the contact pads (425) to a via (440); and/or the contact pads (425) themselves can be electrically coupled to their respective vias (440) without the use of traces (435) (interpreted as each constriction comprising a detection device, claim 1) (col 6, lines 5-11). Shkolnikov teaches that Figure 6 is a perspective view of a microfluidic channel (600) according to an example of the principles described herein, which includes a narrowed portion (605) along the length of the microfluidic channel (600) (interpreted as a constriction, claim 1) (col 9, lines 9-13; and Figure 6). Figure 6 is shown below:
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Shkolnikov teaches that the dimensions of the narrowed portion (605) of the microfluidic channel (600) can be varied based on the type of cell to be porated by the electrodes (610) (interpreted as constrictions having different shapes, claim 7) (col 9, lines 26-28). Shkolnikov teaches that the die (410) can have a first upstream portion (705) that can include any number of microfluidic channels, reservoirs, and/or pumps, among other microfluidic devices, wherein the cells can pass through or by a number of devices to prepare the cell for poration by the electrodes (610) and/or transport the cells through the narrowed portion (605) of the microfluidic channel (600) (interpreted as comprising a plurality of constrictions, each comprising a detection device, claim 1) (col 9, lines 51-57).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the cell electroporation and molecular delivery system comprising microfluidic channels comprising constrictions, electrode sensors, detectors, lock-in amplified, bandpass filter, etc. as disclosed by Zahn to include the ejector as taught by Shkolnikov with a reasonable expectation of success in detecting a specific cell type within a cavity; in selectively identifying, collecting, and/or dispensing a porated cell in the microfluidic system such as within a cassette into a well of a well plate or discard the cell to waste; and/or in delivering a molecule into each of the cells identified and/or selected.
The combined references of Zahn and Shkolnikov do not specifically exemplify a channel having additional constriction shapes (claim 7, in part).
Regarding claim 7 (in part), Sano teaches that the mechanical properties of a cell, which include parameters such as elasticity, inner pressure, and tensile strength, are extremely important because changes in these properties are indicative of diseases ranging from diabetes to malignant transformation, such that considering the heterogeneity within a population of cancer cells, a robust measurement system at the single cell level is required for research and in clinical purposes, wherein a potential microfluidic device for high-throughput and practical mechanotyping were developed to investigate the deformability and sizes of cells through a single run, wherein this mechanotyping device consisted of two different sizes of consecutive constrictions in a microchannel and measured the size of cells and related deformability during transit, such that cell deformability was evaluated based on the transit and on the effects of cytoskeleton affecting drugs, which were detected within 50 ms (interpreted as a series of constrictions of different shapes/sizes, claim 7) (Abstract). Sano teaches that cell mechanotyping has shown great potential in the early diagnosis and prognosis of cancer metastasis and may have potential applications in regenerative medicine and cell transplantation (pg. 1290, col 1, first partial paragraph, lines 4-8). Sano teaches in Figure 1, an overview of the experimental setup of the mechanotyping device based on an electrical detection system including: (a) an image of the experimental setup consisting of the mechanotyping device, electrodes, and a tube for withdrawing solution; (b) an image of the mechanotyping device comprising PDMS microfluidic channels and a glass slide coverslip; (c) a magnified image of the mechanotyping device, where the numbers in green show the reservoirs, and reservoir 2 was connected to a syringe pump; (d) an image of the consecutive constriction channel taken using a microscope, wherein the dimensions of the channel and the positions of the reservoirs’ are shown in the image; and (e) a constant electric field (depicted in red) was applied across the detection area to maintain an electrical steady state for current measurement and to drive samples into the detection area (interpreting Figure 1 to show constrictions comprising different shapes in series, claim 7) (pg. 12891, Figure 1). Figure 1 (in part) is shown below:
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Sano teaches combining a 6 µm wide, 200 µm long, and 9.6 µm high microchannel with a dual photodiode detection system enabled the transit time required for a cell to pass through the constriction area to be measured (pg. 12891, col 1, first partial paragraph, lines 9-12). Sano teaches using the cell deformability measurements, the expression level of lamin A was determined to have a significant effect on the mechanical properties of the cells; and that most of the aforementioned assay techniques rely on optical detection systems, such as high-speed CCD imaging, hence, their spatial resolution is limited to a few µm in the xy plane; as well as, using resistive-pulse sensing (RPS) as a potential alternative method, which is based on the detection of the ionic current blocking created when a particle transits a micropore or microchannel, wherein high signal-to-noise ratios were obtained using a single channel size by isolating the detection circuit from the electrophoretic circuit (pg. 1289, col 2, first partial paragraph; and last partial paragraph). Sano teaches that two different widths of constrictions were placed in a single detection microchannel to simultaneously enable cell sizing and deformability measurements using RPS as shown in Figure 1 (interpreted as constrictions comprising different shapes in series, claim 7) (pg. 12892, col 1, last partial paragraph, lines 1-4). Sano teaches the development of a system for the simultaneous detection of an ionic current and optical signal, wherein the device consists of two power supplies for electrophoresis and ionic current detection, that is, an ammeter and a resistive element, such that the resistance of the detection cell increases as the cell passes through the detection channel and, thus, the current bypasses the detection channel through the detection circuit (pg. 12892, col 2, last partial paragraph).
It is prima facie obvious to combine prior art elements according to known methods to yield predictable results; the court held that, "…a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of skill in the art. KSR International Co. v. Teleflex Inc., 550 U.S. ___, ___, 82 USPQ2d 1385, 1395 (2007); Sakraida v. AG Pro, Inc., 425 U.S. 273, 282, 189 USPQ 449, 453 (1976); Anderson’s-Black Rock, Inc. v. Pavement Salvage Co., 396 U.S. 57, 62-63, 163 USPQ 673, 675 (1969); Great Atlantic & P. Tea Co. v. Supermarket Equipment Corp., 340 U.S. 147, 152, 87 USPQ 303, 306 (1950)”. Therefore, in view of the benefits of using a microfluidic system to subject cells to mechanical deformation as exemplified by Sano, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the system, methods, and fluidic devices including detectors, electrodes, lock-in amplifier, channels, processors, etc. for cell electroporation and molecular delivery as disclosed by Zahn, along with the cassette, cell ejector, and sensors for detecting any cell type within any cavity of the die for selective ejection and/or dispensing of a cell as taught by Shkolnikov to include the series of constrictions comprising different shapes including different widths of constrictions; as well as, a system for the simultaneous detection of an ionic current and optical signal, wherein the device consists of two power supplies for electrophoresis and ionic current detection, and detection via optical detection and resistive pulse sensing as taught by Sano with a reasonable expectation of success in identifying and differentiating different cell types in a sample by their physical and/or biological parameters including by size, impedance, conductivity, elasticity, inner pressure, tensile strength, etc.; in determining the presence of a specific type of cell in a sample, and selectively ejecting, isolating and/or collecting a specific cell type into a well plate including cancer cells, induced pluripotent stem cells (iPS) and/or adult human mesenchymal stem cells; in delivering a molecule into each of the plurality of cells focused within a detection area; and/or in using a single channel to attain high signal-to-noise ratios.
Thus, in view of the foregoing, the claimed invention, as a whole, would have been obvious to one of ordinary skill in the art at the time the invention was made. Therefore, the claims are properly rejected under 35 USC §103(a) as obvious over the art.
The Examiner suggests that Applicant amend claim 1 to specifically identify or exemplify the very broadly recited components.
Conclusion
Claims 1-7 remain rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY M BUNKER whose telephone number is (313) 446-4833. The examiner can normally be reached on Monday-Friday (6am-2:30pm).
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/AMY M BUNKER/
Primary Examiner, Art Unit 1684
Prosecution Insights