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 .
Status of Claims
Current pending claims in the claim set submitted on 25 FEBRUARY 2026 are Claims 1-5 and 15-25 and are considered on the merits below.
Claims 1 and 16 are ‘Currently Amended’; Claims 2-5, 15 and 17-25 are ‘Original’; Claims 6-14 and 26-27 are ‘Withdrawn’.
Response to Amendment/Response to Arguments
Applicant’s arguments, see REMARKS, filed 25 FEBRUARY 2026, with respect to the 112(b) rejection have been fully considered and are persuasive. The 112(b) rejection has been withdrawn.
In response to Applicant’s amendments, the grounds for the previously pending claim are modified compared to the previous actions which include in part rely on the same prior art.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-5 and 5-25 are rejected under 35 U.S.C. 103 as being unpatentable over XING, X et al, Dielectrophoretic isolation of cells using 3D microelectrodes featuring castellated blocks, Analyst, 2015, 140, 3397-3405, in view of Xing, NG, Chun Ning et al, Railing cells along 3D microelectrode tracks for continuous-flow dielectrophoretic sorting, Lab Chip,2018,18,3760, submitted on the Information Disclosure Statement on 23 JANUARY 2024; Non-Patent Literature Documents Cite No. 8, and further in view of TANG, MULTIFUNCTIONAL 3D VIADUCT MICROELECTRODES FOR CONTINUOUS-FLOW DIELECTROPHORETIC RAILING AND ELECTROPORATION OF CELLS UNDER MODULATED ACTIVATION, Transducers 2021 Virtual Conference 20 - 24 June 2021.
Applicant’s invention is directed to a device, a flow-through microfluidic apparatus for cell treatment.
Regarding Claim 1, the reference XING discloses a flow-through microfluidic apparatus for cell treatment, abstract, Figure 1(a), comprising:
a flow chamber, Figure 1(a), page 3398; and
a three-dimensional (3D) microelectrode array disposed in the flow chamber and configured to produce electrical fields for cell
wherein the flow chamber comprises a sample flow region, a first sheath flow region, and a second sheath flow region, Figure 1(a-c), page 3398, Figure 2(a), page 3400, isolation trenches/gap seen in instant drawings Figure 1A create sheath regions; wherein the sample flow region has a first input allowing a sample flow of a plurality of cells and one or more exogenous agents to enter the sample flow region, Figure 1(a), page 3398, inlet, page 3399, Section ‘Cells and reagents’, a first output allowing cells that are damaged to exit from the flow chamber, Figure 1(a), including page 3398, outlet for separating viable and nonviable cells, page 3399, Section ‘Cells and reagents’, and a first fluid channel region having a first path defined therein between the first input and the first output and configured for the cells and the exogenous agents to flow, Figure 1(a-c), page 3398, outlet, page 3399, Section ‘Cells and reagents’, Figure 2(a), page 3400, middle section (in color version, burgundy colored section); an output configured to allow viable transfected cells to exit from the flow chamber, page 3398, left column, page 3399, Section ‘Measurements’.
Examiner Note: It should be noted that language that recites ‘the sample flow region … allowing a sample flow of a plurality of cells and one or more exogeneous agents to enter the sample flow region’ is directed to language of the material worked upon or put into the device. The “[i]nclusion of the material or article worked upon by a structure being claimed does not impart patentability to the claims.” In re Otto, 312 F.2d 937, 136 USPQ 458, 459 (CCPA 1963); see also In re Young, 75 F.2d 996, 25 USPQ 69 (CCPA 1935). Examiner interprets that as long as the flow region accepts a sample to allow a sample to enter the claim language has been satisfied. Nothing structurally further defines or is specific to cells and one or more exogeneous agents.
The XING reference discloses the claimed invention, but is silent in regards to the input and output of the sheath flows.
The NG reference discloses a flow-through microfluidic apparatus for cell treatment, abstract, microfluidic device, comprising:
a flow chamber, Figure 1(a), page 3761; and
a three-dimensional (3D) microelectrode array disposed in the flow chamber, Figure 1(a), page 3761, and configured to produce electrical fields for cell
wherein the flow chamber comprises a sample flow region, a first sheath flow region, and a second sheath flow region, Figure 1(a), page 3761, including left and right columns;
wherein the sample flow region has a first input allowing a sample flow of a plurality of cells and one or more exogenous agents to enter the sample flow region, Figure 1(a), page 3761, ‘Sample’, page 3762, Section: Cells and reagents, Experimental, first output allowing cells that are damaged to exit from the flow chamber, and a first fluid channel region having a first path defined therein between the first input and the first output and configured for the cells and the exogenous agents to flow, Figure 1(a), 3761, HCT116 cells in green;
wherein the first sheath flow region has a second input configured to allow a first sheath flow to enter the first sheath flow region, Figure 1(a), page 3761, a second output configured to allow viable transfected cells to exit from the flow chamber, and a second fluid channel region having a second path defined therein between the second input and the second output and configured for the first sheath flow to flow, Figure 1(a), page 3761, including text on page 3761, outlet I and II;
wherein the second sheath flow region has a third input configured to allow a second sheath flow to enter the second sheath flow region and a third output to allow the second sheath flow to exit from the second sheath flow region, Figure 1(a), page 3761, including text on page 3761, page 3762-3763, Section: Device; and
wherein the same 3D microelectrode array that rails the cells is further configured to apply pulses to the railing cells the concurrently dielectrophoretically sort viable cells from damaged cells, such that damaged cells experience a weakened dielectrophoretic (DEP) force and are released from microelectrode tracks, page 3767, Continuous-flow cell sorting, right column.
It would be obvious to one having ordinary skill in the art before the effective filing date to modify the XING reference with the sheath input (second and third inputs) and output (second and third outputs) as taught by NG to achieve continuous-flow cell sorting at a higher performance, often both in terms of efficiency and flow rate, than that achieved by guiding cells through thin film surface electrodes, page 3768, Section : Conclusion.
The combination above suggests the claimed invention, but is silent in regards to wherein the three-dimensional (3D) electrode array disposed in the flow chamber and configured to produce electrical fields for cell railing, electroporation and sorting.
The TANG reference discloses a flow-through microfluidic apparatus for cell treatment, Figure 1(a), page 695, comprising:
a flow chamber, Figure 1(a), page 695; and
a three-dimensional (3D) microelectrode array disposed in the flow chamber, Figure 1(a), page 695, abstract, multifunctional silicon 3D viaduct electrodes, page 695, Section : Introduction, and configured to produce electrical fields for cell railing, abstract, page 695, Section Introduction, Theory, Figure 1(b), electroporation, abstract, page 695-696, Section : Introduction, Theory, Methods: Experiment, and sorting, page 695, abstract, Introduction, page 698, Results: Cell Electroporation;
wherein the flow chamber comprises a sample flow region and a first sheath flow region, page 695, Figure 1(a-b), Section : Introduction;
wherein the sample flow region has a first input allowing a sample flow of a plurality of cells and one or more exogenous agents to enter the sample flow region, a first output allowing cells that are damaged to exit from the flow chamber, and a first fluid channel region having a first path defined therein between the first input and the first output and configured for the cells and the exogenous agents to flow, page 695, Figure 1(a-c);
and wherein the same 3D microelectrode array that rails the cells is further configured to apply electroporation pulses to the railing cells and to concurrently dielectrophoretically sort viable electroporated cells from damaged cells, such that damaged cells experience a weakened dielectrophoretic (DEP) force and are released from microelectrode tracks, page 695-696, Section : Introduction, Theory, page 697-698, Results and Conclusion, Figure 1(a-c).
It would be obvious to one having ordinary skill in the art before the effective filing date to modify the XING and NG refence with the 3D microelectrode array of TANG which teaches all of cell railing, electroporation and sorting that shows the potential for continuous-flow rapid cell flow, i.e uninterrupted sample flow while maintaining continuity, page 695, Introduction.
Additional Disclosures Included are: Claim 2: wherein the flow-through microfluidic apparatus of claim 1, wherein the 3D microelectrode array is disposed to be inclined at a predetermined angle with respect to a flow direction of the flow chamber, NG, Figure 1(a), page 3761, XING angles in Figure 1(a-c), Figure 2(b-d), TANG Figure 1(a-c), page 695, Section : Introduction, Theory. ; Claim 3: wherein the flow-through microfluidic apparatus of claim 2, wherein the predetermined angle is in a range between about 0° and about 90°, NG, Figure 1(a), page 3761, 3761, ‘Dielectrophoretic railing of cells’; XING, angles in Figure 1(a-c), Figure 2(b-d), TANG, Figure 1(a). ; Claim 5: wherein the flow-through microfluidic apparatus of claim 1, wherein the first sheath flow and the second sheath flow each includes dielectrophoretic buffer, XING page 3399, Sections ‘Cells and reagents’ and ‘Measurements’, NG Figure 1, DEP buffer, page 3761, Section : Cells and reagents, page 3762.; Claim 15: wherein the flow-through microfluidic apparatus of claim 1, wherein the three-dimensional (3D) microelectrode array comprises a microelectrode unit comprising a microelectrode pillar and a microelectrode track disposed on a top surface of the microelectrode pillar, XING Figure 1(a-c), page 3398, blue structure, NG Figure 1(a), page 3761, page 3761-3762, Section: Device fabrication, TANG Figure 1(a-c), page 695.; Claim 16: wherein the flow-through microfluidic apparatus of claim 15, wherein a space of a rectangular or oval shape is formed between the microelectrode pillar and the microelectrode main body, XING Figure 2 (d and e), Figure 5(a), NG, Figure 1(a), passages are of oval shape, TANG Figure 1(b), Figure 2(a), page 696, Section : Methods: Fabrication. ; Claim 17: wherein the flow-through microfluidic apparatus of claim 1, wherein the three-dimensional (3D) microelectrode array comprises one or more microelectrode units formed with an interdigitated pattern, each microelectrode unit being formed in a shape of a viaduct having a plurality of micro-arches, XING page 3399-3400, Sections ‘Devices’ and ‘Design’, Figure 2, NG abstract, page 3762, Section: Device, TANG Figure 1(a-c), page 695.; Claim 18: wherein the flow-through microfluidic apparatus of claim 17, wherein each micro-arch of the plurality of micro-arches has a shape of an oval, XING page 3399-3400, Sections ‘Devices’ and ‘Design’, Figure 2 and 5(a), NG, Figure 1(a), passages are of oval shape, TANG Figure 1(a-c), page 695.; Claim 19: wherein the flow-through microfluidic apparatus of claim 17, wherein each microelectrode unit of the one or more microelectrode units comprises a plurality of microelectrode pillars spaced apart from each other and a plurality of connecting microelectrode tracks disposed on top surfaces of the microelectrode pillars and interconnecting adjacent microelectrode pillars, XING Figures 1(a-d) and Figure 2 (a-d), NG, abstract, Figure 1(a), page 3761, TANG Figure 2(a).; Claim 20: wherein the flow-through microfluidic apparatus of claim 19, wherein a width of any one of the microelectrode tracks connecting two adjacent microelectrode pillars gradually decreases from centers of the adjacent microelectrode pillars to centers of spaces between the adjacent microelectrode pillars, XING Figures 1(a-d) and Figure 2(b-d), Figures 3(a-c), NG Figure 1(a), page 3761, Figure 2(a-d), page 3763, TANG Figure 1(b) and 2(b-c).; Claim 21: wherein the flow-through microfluidic apparatus of claim 17, wherein the one or more microelectrode units comprise microelectrode units in pairs, XING page 3399, Section: Designs, NG, Figure 1(a), page 3761, TANG Figure 1(a).; Claim 22: wherein the flow-through microfluidic apparatus of claim 1, wherein the 3D microelectrode array is made of single crystal silicon, abstract, single crystal silicon, XING page 3399, Section ‘Devices’, NG page 3762, Section : Device, page 696 Section: Methods, Fabrication Figure 2(a).; Claim 23: wherein the flow-through microfluidic apparatus of claim 1, wherein the 3D microelectrode array is made of single crystal silicon by tailoring dry etch profile, XING abstract, page 3398, left column, page 3399, Section ‘Devices’, NG page 3761-3762, Section: Device fabrication, page 696 Section: Methods, Fabrication Figure 2(a). Examiner Note: method of making has no patentable weight on claimed invention; product by process; and Claim 24: wherein the flow-through microfluidic apparatus of claim 1, wherein the 3D microelectrode array is built into a device layer of a silicon-on-insulator substrate, XING page 3399-3400, Section ‘Design’, NG, page 3761-3762, Section: Device fabrication, page 696 Section: Methods, Fabrication Figure 2(a).
Regarding Claim 4, the XING reference discloses the claimed invention, but is silent in regard to wherein the flow-through microfluidic apparatus of claim 3, wherein the predetermined angle is in a range between about 7° and about 26°.
However, NG does teach the flow-through microfluidic apparatus of claim 3, wherein the predetermined angle is in a range between about 7° and about 26°, Figure 4, page 3764, Section : Dielectrophoretic railing of cells. XING, however, does teach that the three-dimensional (3D) microelectrode array, Figure 1(a), page 3398, are formed through etching, extruded metals through electroplating, or an array of carbon posts through resist pyrolysis, page 3398, and can be seen in Figure 1(a) the angle is at 90°.
In addition, TANG discloses the wherein the flow-through microfluidic apparatus of claim 3, wherein the predetermined angle is in a range between about 7° and about 26°, TANG, Figure 1(a).
Since XING teaches methods of manufacturing the array, it would be obvious to one having ordinary skill in the art before the effective filing date to use the known techniques of manufacturing the array to be manufactured at a predetermined angle is in a range between about 7° and about 26° with respect to the flow directed to optimize separations, manipulations, sorting, handling and positioning, page 3397.
Regarding Claim 25, the combination of XING , NG, and TANG suggests the claimed invention. While XING is silent in regards to microelectrode array is built into a thin silicon wafer bonded over an insulating substrate, NG teaches the flow-through microfluidic apparatus of claim 1, wherein the 3D microelectrode array is built into a thin silicon wafer bonded over an insulating substrate, NG, page 3761-3762 and 3768, Section: Device fabrication, Conclusion and TANG teaches wherein the 3D microelectrode array is built into a thin silicon wafer bonded over an insulating substrate, page 696 Section: Methods, Fabrication Figure 2(a).
It would be obvious to one having ordinary skill in the art before the effective filing date to have the microelectrode array is built into a thin silicon wafer bonded over an insulating substrate as taught by NG and TANG to leverage the insulating layer to isolate the circuits, which enhances performance by reducing unwanted capacitance and improving speed and power efficiency and provide improved thermal management, enhanced stability, and greater reliability.
Conclusion
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 CHRISTINE T MUI whose telephone number is (571)270-3243. The examiner can normally be reached M-Th 5:30 -15:30 EST.
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CTM
/CHRISTINE T MUI/Primary Examiner, Art Unit 1797