Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant's election with traverse of Group I, Species A (claims 1-7) in the reply filed on 04/08/2026 is acknowledged. The traversal is on the ground(s) that the apparatus of claims 1-7 is specifically designed for carrying out the method of claims 8-11, as both share the same inventive concept of using a fluidic pump disposed within a microfluidic channel to direct cells through a constriction region for transfection.. This is not found persuasive because the technical feature of a constriction region through which cells flow, this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of European Patent No. EP353663A1 to Lu et al. (cited by applicant). Lu et al. discloses and apparatus that comprises a reservoir to store a biologic sample containing a cell ([0042], [0052]-[0053]) and a microfluidic channel fluidically that is coupled to the reservoir. The microfluidic channel includes a constriction region including a circumference that is attenuated from remaining portions of the microfluidic channel ([005], [0062], fig.18), and a fluidic pump disposed within the microfluidic channel ([0065]) to direct flow of the cell from the reservoir to the microfluidic channel and through the constriction region ([0009], [0057]).
The requirement is still deemed proper and is therefore made FINAL.
Claims 8-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 04/08/2026.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-7 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1, line 2 recites a first reservoir “to store” a biologic sample containing a cell. As such, claim 1 does not actually recite that a biologic sample containing a cell is stored in the first reservoir. Accordingly, the recitation of “the cell” in the body of claim 1 and the dependent claims lack sufficient antecedent basis in the claims.
Claim 2 recites “the cell membrane” in line 4. There is insufficient antecedent basis for this limitation in the claim.
Claim 4, lines 2-3 recites the second reservoir “to store” transfection material. As such, claim 4 does not actually recite that transfection material is stored in the second reservoir. Accordingly, the recitation of “the transfection material” in the body of claim 4 and the dependent claims lack sufficient antecedent basis in the claims.
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)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
1. Claims 1-6 are rejected under 35 USC 102(a)(2) as being anticipated by International Patent Application Publication No. WO2020263218 to Shkolnikov et al. (cited by applicant)
Shkolnikov et al. teaches a cell transfection device that includes a transfection chip (Figs. 1-4) that includes a reservoir (cell source 102/202 (Figs, 1-4) that stores a biologic sample containing cells. microfluidic channel [0023] that includes a transfection chamber 112 that operates through constriction that may induce poration of the membrane of a cell. A constricting design shrinks the size of the channel to a size small enough so that the edges of the chamber exert physical pressure on the cell within the transfection chamber 112. The increased constriction pressure results in sufficient poration of the cell membrane to enable transfection (of transfection material). [0027]
Shkolnikov et al. further teaches an inertial pump using microfluidic ejectors located inside the fluidic channel for moving fluid through the channel. [0039]
Shkolnikov et al. further teaches that a pump system is provided on the chip outlet 302 and that electronics are provided to operate the pump system. [0030]
I.) Regarding applicant’s claim 1, as noted above, Shkolnikov et al. teaches all the elements of claim 1.
Therefore, Shkolnikov et al. anticipates claim 1.
II.) Regarding applicant’s claim 2, as noted above, Shkolnikov et al. anticipates claim 1 from which claim 2 depends.
Claim 2 recites that the circuitry is to activate the fluidic pump to direct the flow of the cell to: apply shear force on the cell in response to the flow through the constriction region, and thereby cause formation of apertures in the cell membrane of the cell; and expose the cell to transfection material to transfect the cell.
As noted above Shkolnikov et al. further teaches an inertial pump using microfluidic ejectors located inside the fluidic channel for moving fluid through the channel.
As further noted above, Shkolnikov et al. teaches a transfection chamber 112 that operates through constriction that may induce poration of the membrane of a cell. A constricting design shrinks the size of the channel to a size small enough so that the edges of the chamber exert physical pressure on the cell within the transfection chamber 112. The increased constriction pressure results in sufficient poration of the cell membrane to enable transfection (of transfection material). [0027]
Therefore, Shkolnikov et al. anticipates claim 2.
III.) Regarding applicant’s claim 3, as noted above, Shkolnikov et al. anticipates claim 1 from which claim 3 depends.
Claim 3 recites fluidic pump includes a plurality of resistors disposed within the microfluidic channel, and the circuitry is to selectively activate the plurality of resistors to provide a first flow rate to flow the cell to the microfluidic channel and provide a second flow rate to flow the cell into and through the constriction region, wherein the second flow rate includes a change in velocity from the first flow rate.
Shkolnikov et al. teaches that In an example, the microfluidic ejector 704 can be a thin-film resistors capable of producing sufficient heat to fire a droplet containing the transfected cell 512 through the drop ejector orifice 706.
Due to the change in diameter from the channel upstream of the constriction and in the constriction, using the resistors cause fluid to flow in the transfusion chip would provide a first flow rate to flow the cell to the microfluidic channel and provide a second flow rate to flow the cell into and through the constriction region, wherein the second flow rate includes a change in velocity from the first flow rate.
Therefore, Shkolnikov et al. anticipates claim 3.
IV.) Regarding applicant’s claim 4, as noted above, Shkolnikov et al. anticipates claim 1 from which claim 4 depends.
Claim 4 recites a second reservoir fluidically coupled to the microfluidic channel, the second reservoir to store transfection material; and wherein the circuitry is to activate the fluidic pump to: direct the flow of the cell from the first reservoir to the microfluidic channel and through the constriction region and direct flow of the transfection material from the second reservoir to the microfluidic channel and through the constriction region to transfect the cell.
Shkolnikov et al. teaches single cell transfection with interchangeable reagent (Abstract). The reagent (transfection material) is provided in reagent receiver 602 (second reservoir) which is directed into the channel 104 in which the cells having sufficient poration for transfection are fed as show in Fig. 9.
Therefore, Shkolnikov et al. anticipates claim 4.
V.) Regarding applicant’s claim 5, as noted above, Shkolnikov et al. anticipates claim 1 from which claim 5 depends.
Claim 5 recites the microfluidic channel includes a first channel including the constriction region and a second channel that intersects and is in fluidic communication with the first channel, the fluidic pump being disposed within the second channel.
In reference to moving fluid into the transfection chamber 112 from the fluidic channel 104, cell reservoir 502, and reagent receiver 602 Shkolnikov et al. teaches that in an example, another mechanism for movement of the fluid through the fluidic channel 104 towards the transfection chamber 112 is a T-pump including a microfluidic ejector located in a pocket connecting to but out of the direct path of the fluidic channel 104. [0039]
Therefore, Shkolnikov et al. anticipates claim 5.
VI.) Regarding applicant’s claim 6, as noted above, Shkolnikov et al. anticipates claim 1 from which claim 6 depends.
Claim 6 recites that ejection nozzle disposed within the microfluidic channel, wherein the circuitry is to activate a resistor of the ejection nozzle to eject the cell from the microfluidic channel to a chamber, wherein the chamber includes transfection material, and in response, exposes the cell to the transfection material.
Shkolnikov et al. teaches a mechanism of the microfluidic ejection chamber may also aid in moving the fluid into the transfection chamber 112 from the cell reservoir 502. [0038] The ejection involves propelling fluid through an orifice (ejection nozzle). [0038]
Therefore, Shkolnikov et al. anticipates claim 6.
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.
2. Claims 1 and 7 are rejected under 35 USC 102(a)(1) as being anticipated by European Patent Application Publication No. EP3539663 to Lu et al. (cited by applicant)
Lui et al. teaches an apparatus for testing cells and particles that includes a microfluidic channel that is coupled to a reservoir that contains a sample holding chamber (first reservoir) 1021 ([0045]), a microfluidic channel 36 ([0005]), and constriction regions 1140 (Fig. 13). A pump 1160 draws fluid from microfluidic reservoir 1134 into channel 1136. Pump 1160 further circulates fluid that has passed through constriction 1140 and across sensor 1138. [0065] Lu et al. teaches that a controller and circuitry are provided to operate the device. [0009]
I.) Regarding applicant’s claim 1, as noted above Lu et al, teaches all the elements of claim 1.
Therefore, Lu et al. anticipates claim 1.
II.) Regarding applicant’s claim 7, as noted above Lu et al. anticipates claim 1 from which claim 7 depends.
Claim 7 recites that microfluidic channel includes a first channel including the constriction region and a second channel including a second constriction region, wherein the second constriction region includes a second circumference that is attenuated from remaining portions of the microfluidic channel and wherein the first constriction region and the second constriction region include different dimensions from one another; and the circuitry is to activate the fluidic pump to: direct the flow of the cell from the first reservoir to the first channel and through the constriction region; and direct flow of a second cell from the first reservoir to the second channel and through the second constriction region.
Lu et al. teaches that the microfluidic channel includes two portions that have constriction regions 1140 that “may be differently sized such that particles or cells of a first size more readily flow through.” [0060]
Therefore, Lu et al. anticipates claim 7.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
3. Claim 7 is rejected under 35 USC 103 as being unpatentable over Shkolnikov et al.
I.) Regarding applicant’s claim 7, as noted above, Shkolnikov et al. anticipates claim 1 from which claim 7 depends.
Claim 7 recites that microfluidic channel includes a first channel including the constriction region and a second channel including a second constriction region, wherein the second constriction region includes a second circumference that is attenuated from remaining portions of the microfluidic channel and wherein the first constriction region and the second constriction region include different dimensions from one another; and the circuitry is to activate the fluidic pump to: direct the flow of the cell from the first reservoir to the first channel and through the constriction region; and direct flow of a second cell from the first reservoir to the second channel and through the second constriction region.
In Fig. 9 Shkolnikov et al. depicts an embodiment in which the microfluidic channel includes a first channel including the constriction region and a second channel including a second constriction region, wherein the second constriction region includes a second circumference that is attenuated from remaining portions of the microfluidic channel and the circuitry is to activate the fluidic pump to: direct the flow of the cell from the first reservoir to the first channel and through the constriction region; and direct flow of a second cell from the first reservoir to the second channel and through the second constriction region.
Shkolnikov et al. teaches cells that have different diameters and can be performed using constrictions of different diameters. [0021], [0023]
Shkolnikov et al. does not teach an embodiment that includes first constriction region and a second constriction region with different dimensions from one another to process cells that have different diameters.
It would have been obvious to one of ordinary skill in the art before applicant’s effective filing date to modify Shkolnikov et al. to provide a first constriction region and a second constriction region with different dimensions from one another to process cells that have different diameters.
Therefore, Shkolnikov et al. renders claim 7 obvious.
4. Claim 1 is rejected under 35 USC 103 as being unpatentable over International Patent Application Publication No. WO2021/015778 to Govyadinov et al. in view of Lu et al.
Govyadinov et al. teaches a cell poration and transfection apparatus that includes a reservoir (block 102) for storing cells. [0016]. The cells flow though channel 208 to a constriction region where the sidewalls 224 may constrict the cell 204 as the cell 204 moves between the sidewalls 224. [0033].
Govyadinov et al. teaches that the cells are delivered from the reservoir by a pump [0016] , but does not specifically teach that the pump is in the microfluidic channel or that the pump is controlled by circuitry that activates the pump.
As noted above, Lu et al. teaches an apparatus for testing cells and particles that includes a microfluidic channel that is coupled to a reservoir that contains a sample holding chamber, a microfluidic channel constriction regions and a pump draws fluid from microfluidic reservoir into channel.
It would have been obvious to one of ordinary skill in the art before applicant’s effective filing date to modify Govyadinov et al. to include a pump that draws fluid from microfluidic reservoir into channel (i.e., in the microfluidic channel) as taught by Lu et al. and circuitry to control the pump as a matter of a simple substitution of one known element for another to obtain predictable results. (MPEP2143(I)(B)).
Therefore, Govyadinov et al. in view of Lu et al. renders claim 1 obvious.
5. Claims 1 and 2 are rejected under 35 USC 103 as being unpatentable over U.S. Patent Application Publication No. 2014/0287509 to Sharei et al. in view of Lu et al.
Sharei et al teaches an intercellular delivery device that includes an inlet reservoir that supplies cells to a microfluid channel 10 and through a constriction region 15. [0091], [0176]
Sharei et al teaches a pressure pump, a gas cylinder, a compressor, a vacuum pump, a syringe, a syringe pump, a peristaltic pump, a manual syringe, a pipette, a piston, a capillary actor, and gravity, but does not teach a pump in the microfluidic channel. [0011].
As noted above, Lu et al. teaches an apparatus for testing cells and particles that includes a microfluidic channel that is coupled to a reservoir that contains a sample holding chamber, a microfluidic channel constriction regions and a pump draws fluid from microfluidic reservoir into channel.
It would have been obvious to one of ordinary skill in the art before applicant’s effective filing date to modify Sharei et al. to include a pump that draws fluid from microfluidic reservoir into channel (i.e., in the microfluidic channel) as taught by Lu et al. and circuitry to control the pump as a matter of a simple substitution of one known element for another to obtain predictable results. (MPEP2143(I)(B)).
Therefore, Sharei et al. in view of Lu et al. renders claim 1 obvious.
II.) Regarding applicant’s claim 2, as noted above, Sharei et al. in view of Lu et al. renders claim 1 obvious from which claim 2 depends.
Claim 2 recites that the circuitry is to activate the fluidic pump to direct the flow of the cell to: apply shear force on the cell in response to the flow through the constriction region, and
thereby cause formation of apertures in the cell membrane of the cell; and expose the cell to transfection material to transfect the cell.
Sharei et al. teaches that the constriction region causes perturbations the membrane of the cells and that allow to transfection material to transfect the cells. [0090], [0182]
Therefore, Sharei et al. in view of Lu et al. renders claim 2 obvious.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
International Patent Application Publication No. WO2021/126262 to D'Apuzzo et al. discloses a thermal resistor which, upon receiving electrical current, heats to a temperature above the nucleation temperature of the fluid so as to vaporize a portion of the adjacent fluid to create a bubble which displaces the fluid through the associated orifice. [0030]
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/MICHAEL STANLEY GZYBOWSKI/Examiner, Art Unit 1798
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