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 .
Election/Restriction
Applicant's election with traverse of Claims 2-9, 11-15, and 29-31 in the reply filed on 10/6/2025 is acknowledged. The traversal is on the grounds that the Examiner has provided no grounds for restriction between Invention II and Invention III, and thus the Applicant respectfully traverses the restriction at least as it pertains to restriction between Invention II and Invention III. This is not found persuasive because the inventions are distinct and separate from the originally presented claims and are therefore not eligible to receive an action on the merits.
Invention II (Claim 32) is related to Invention I as combination and subcombination. In the instant case, the combination as claimed does not require the particulars of the subcombination as claimed because Invention I does not require at least one active agent chamber, wherein the reaction chamber is distinct from the at least one active agent chamber. The subcombination has separate utility such as maintaining separate storage of an active agent within the reaction unit where the active agent never contacts a sample within the reaction unit because the active agent is not loaded in situ.
Invention III (Claim 33) is also related to Invention I as combination and subcombination. In the instant case, the combination as claimed does not require the particulars of the subcombination as claimed because Invention I does not require the plurality of seeding ports that prevent flow of the cell sample. The subcombination has separate utility such as capturing a cell sample for observation following exposure to an active agent that is loaded during operations and not in situ.
Claims 16-28, 32, and 33 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 10/6/2025.
The requirement is still deemed proper and is therefore made FINAL.
Response to Amendment
This is an office action in response to applicant's arguments and remarks filed on 10/6/2025. Claims 2-9, 11-15, and 29-31 are pending in the application.
Status of Objections and Rejections
All rejections from the previous office action are maintained.
Response to Arguments
Applicant's arguments filed 10/6/2025 have been fully considered but they are not persuasive.
On Page 26 of the Remarks, the Applicant argues that there is no disclosure nor suggestion whatsoever in Maerkl of the valves 4406 providing one type of flow and preventing another type of flow at one and the same time, which are mutually incompatible in Maerkl.
However, the Examiner respectfully disagrees as the invention of Maerkl teaches that the device can be used to mix reagents with a cell and then selectively recover one reagent of interest, see [0279].
On Pages 27-28, the Applicant argues that Maerkl does not teach that the seeding ports provide fluid communication between the respective reaction chamber and a respective group of seeding channels of the second network, and concurrently prevent the flow of cells of a cell sample through the seeding port.
In response to this argument, the examiner respectfully disagrees. The microfluidic device can be used to open the vertical fluidic valves, where a singular valve permits sample flow and another valve permits substrate, or reagent, flow, see [0328].
Regarding the Applicant’s argument on Pages 29-30 that Maerkl is not capable of concurrently preventing cell removal with reagent retention, the Examiner respectfully disagrees as a reagent is flowed into a cell pen/cell chamber and maintained within using the step of compartmentalization. Also, it is unclear how long the reagent and cell are maintained within the chamber within the instant application. Because the prior art reference teaches moments where the reagent is flowed into the cell pen, even if the cell is only retained within the pen for the period of pressurization, then it meets the claim as the limitation has been identified as an intended use of the instant application, specifically acting as a filter. An intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. See In re Casey, 152 USPQ 235 (CCPA 1967) and In re Otto, 136 USPQ 458,459 (CCPA 1963). The apparatus of Maerkl et al. is identical to the presently claimed structure and therefore, would have the ability to perform the use recited in the claim since reagents flow from one channel and sample is deposited using another channel, and the respective seeding ports are capable of preventing and allowing the flow therethrough of sample and reagent (see [0195] – [0196]).
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 2-9, 11-13, 29, and 31 are rejected under 35 U.S.C. 103 as being unpatentable over Maerkl et al. (US 2014/0065653) in view of Gong et al. (US 20030138941) and further in view of Paliwal et al. (US 2015/0355165).
Regarding claim 12, Maerkl et al. teaches a block defining a first plurality of reaction units (elastomeric structure (block) with cell pens 4404 (reaction units), see Fig. 18A-D and [0195]), a first network of feeding channels (horizontal flow channels 4402a for flowing fluid into pen 4404, see Fig. 18A-D and [0196]),
a second network of seeding channels (vertical flow channel 4402b for flowing fluid into pen 4404, see Fig. 18A-F and [0196]), and a control system (pumps 4408 that control flow in microfluidic channels, see Fig. 18A-D and [0195]) for enabling control of fluid flows with respect to the first network of feeding channels and with respect to the second network of seeding channels (para 10 further states a computer controlled external solenoid valves allow actuation);
each said reaction unit being in selective fluid communication with the first network of feeding channels via a respective feeding port, and in selective fluid communication with the second network of seeding channels (cell pen 4404 (reaction unit) is in selective communication with horizontal channels 4402a and vertical channels 4402b via valves 4406, see Fig. 18A-D and [0196]);
each said reaction unit configured, during operation of the platform, for enabling a cell sample to be interacted with a respective active agent (cell pen 4404 (reaction unit) allows a cell to interact with multiple reactants (active agent), see [0326]);
wherein the reaction units contain active agents (cell pen 4404 (reaction unit) stores reacting material (active agents), see [0196], where the material is a single molecule type for identifying a desired molecule, see [0314])
wherein each said reaction chamber comprises a plurality of seeding ports configured for providing free fluid communication between the respective reaction chamber and a respective group of feeding channels of the second network, wherein said seeding ports are configured for preventing flow therethrough of cells of a cell sample while concurrently providing free fluid interchange with respect to the respective reaction unit (vertical channels 4402b (seeding channels) provide fluid to cell pen 4404 (reaction unit) at top and bottom ports (seeding ports), where the vertical ports keep cell G in the pen, see Fig. 18A-D and [0195]- [0196] in Maerkl et al);
wherein each said seeding channel of the respective said group of seeding channels has a respective seeding channel cross-sectional flow area (the seeding channels each have a respective flow area as they allow fluid passage, see [0195]);
wherein an aggregate of said seeding channel cross-sectional flow areas provided by the respective said seeding channels in each said group of seeding channels is at least similar to a cross-sectional flow area provided by the respective said feeding port of the respective reaction unit (the flow channels of the invention are constructed to have the same dimensions, 100 µm wide and 9 µm high, see [0302]); and
wherein the seeding channel cross-sectional flow area of each said respective seeding channel of the respective said group of seeding channels is such as to allow flow of liquids therethrough, and the concurrently prevent flow of the cell sample therethrough, such that each said group of seeding channels operates as a filter to block passage of the cell sample therethrough (the flow channels are capable of opening to only allow entrance to the substrate fluid while maintaining the cell mixture within the cell pen by using the smaller dimension of the channels in comparison to the pen, see Fig. 18 and [0325] – [0328]).
Preventing flow therethrough of cells of a cell sample while concurrently providing free fluid interchange with respect to the respective reaction unit is a limitation with respect to an intended use of the seeding ports. An intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. See In re Casey, 152 USPQ 235 (CCPA 1967) and In re Otto, 136 USPQ 458,459 (CCPA 1963). The apparatus of Maerkl et al. is identical to the presently claimed structure and therefore, would have the ability to perform the use recited in the claim since the channels are capable of opening to only allow entrance to the substrate fluid while maintaining the cell mixture within the cell pen, see [0285]- [0287]).
However, Maerkl does not teach or suggest an embodiment of the invention where each said reaction unit is pre-loaded with a respective pre-determined active agent in situ during manufacture of the microfluidic test platform.
Instead, in the analogous art of microfluidic devices for monitoring a reagent and sample reaction, Gong teaches a microfluidic device containing assay stations with pre-applied reagents, see [0074], where the reagent is a small molecule, see [0086].
It would have been obvious to a person possessing ordinary skill in the art before the effective filing date to have modified the cell pens of Maerkl to include the pre-applied, or pre-loaded, reagents of Gong for the benefit of pre-selecting a library of reagents that react to a cell sample for the monitoring of cell death (see [0231]- [0232] in Gong). Providing dried reagents within an assay chamber was previously known in the art as exemplified by Gong; therefore, the modification of the cell pen of Maerkl to include the pre-loaded reagent of Gong would have had the reasonable expectation of successfully facilitating the mixing of a reagent and a sample to monitor a cell sample’s viability.
Additionally, Maerkl modified by Gong does not teach that each said reaction unit comprises a reaction chamber configured for accommodating therein a cell sample, and at least one active agent chamber, wherein the respective said active agent of the respective reaction unit is accommodated in the respective said at least one active agent chamber.
However, in the analogous art of microfluidic chips for performing cell-based assays, Paliwal et al. teaches a reaction unit comprising a cell chamber configured for accommodating therein a cell sample, and at least one active agent chamber (each reaction unit comprises a test chamber (cell chamber) where a cell sample is kept, and a drug inlet (active agent chamber), see Fig. 8D and [0031]), wherein the respective said active agent of the respective reaction unit is accommodated in the respective said at least one active agent chamber (the drug inlet (active agent chamber) contains drug containing fluids, see [0052]).
It would have been obvious to a person possessing ordinary skill in the art before the effective filing date of the instant application to have modified the cell pen (reaction unit) of Maerkl et al. to include the drug inlet connected to the test chamber for the benefit of maintaining separation between the sample and the active agent, or drug, prior to activation of the valves of the microfluidic platform (see [0052] in Paliwal et al). Additionally, the modification of the reaction unit of Maerkl et al. to include the drug inlet and cell chamber of Paliwal et al. would have had the reasonable expectation of successfully facilitating the reaction between a drug active agent and cell for a cell-based assay.
Regarding claim 2, modified Maerkl teaches the microfluidic test platform according to claim 12, comprising a plurality of microfluidic valves, each microfluidic valve being configured for selectively allowing or preventing flow therethrough under the control of the control system (valves 4406 allow or prevent flow using control lines over valves (control system), see Fig. 18A-D, [0173], and [0195]- [0196] in Maerkl).
Regarding claim 3, modified Maerkl et al. teaches the microfluidic test platform according to claim 12, including at least one of the following; wherein at least one said reaction unit comprises a different said active agent as compared with at least one other said reaction unit (cell pen 4404 (reaction unit) stores material, see [0196], where each chamber contains different chemical species (different active agents), see [0326]).
Regarding claim 4, modified Maerkl et al. teaches the microfluidic test platform according to claim 12, including wherein said active agent comprises any one of: an inorganic or organic molecule, a small molecule, a nucleic acid-based molecule, an aptamer, a polypeptide, or any combinations thereof (the cell pen 4404 (reaction unit) contains a mixture of particles including DNA (nucleic acid-based molecule), see [0311]).
Regarding claim 5, modified Maerkl et al. teaches the microfluidic test platform according to claim 12, including one of the following: wherein said block comprises a block member in overlying fixed relationship with a base member, and wherein said block member comprises an outer- facing first block surface and an outer-facing second block surface, wherein the second block surface is spaced from the first block surface by a block member thickness dimension, and, wherein said block member comprises a material transparent to electromagnetic radiation at least in the visible spectrum (elastomeric structure 24 (block) lies on top of planar substrate 14 (base member) where the elastomeric structure 24 comprises first layer 20 and second layer 22 that are spaced by a small membrane 25 (block member thickness dimension), see Fig. 7A-B and [0083]- [0086], where the elastomeric structure 24 (block) is constructed of PDMS, see [0006], and the elastomer is transparent to light that is visible, see [0171] and [0290]).
Regarding claim 6, modified Maerkl et al. teaches the microfluidic test platform according to claim 12, including: wherein said plurality of said reaction units are arranged in an array with respect to the block of substrate material; wherein said first plurality is an integer greater than 100 (array 4400 comprises a plurality of cell pens 4404 (reaction unit) within the elastomeric structure, see Fig. 18A-D and [0194]- [0195], where the array comprises 256 chambers, see [0279]).
Regarding claim 7, modified Maerkl et al. teaches the microfluidic test platform according to claim 2, wherein said first network is configured for selectively delivering to at least a portion of the reaction units, under the action of the second network, a fluid including at least cell samples (the horizontal flow channel 4402a introduces a cell to the pen 4404 (reaction unit), see [0196]).
Regarding claim 8, modified Maerkl et al. teaches the microfluidic test platform according to claim 7, wherein second network is configured for selectively enabling pockets of said fluids trapped in feeding channel segments of the first network to be urged into the respective reaction units under predefined conditions (vertical flow channels 4402b introduces a fluid into cell pen 4404 (reaction unit) after actuation, see [0196]).
Regarding claim 9, modified Maerkl et al. teaches the microfluidic test platform according to claim 8, wherein the first network comprises a plurality of feeding channels (plurality of horizontal flow channels 4402a, see Fig. 18A-D), each feeding channel being in selective fluid communication with a portion of said reaction chambers via respective said microfluidic valves in the form of respective first microfluidic valves (horizontal channels 4402a is in communication with cell pen 4404 via valve 4406, see Fig. 18A-D and [0196]), wherein each said feeding channel further comprises a plurality of said microfluidic valves in the form of blocking valves, wherein each pair of adjacent blocking valves is configured for selectively isolating a respective said feeding channel segment therebetween from a remainder of the first network (valves 4406 connected to horizontal channels 4402a isolate the flow channel from further cell pens 4404b, see Fig. 18A-D and [0196]).
Regarding claim 11, Maerkl et al. modified by Paliwal et al. teaches the microfluidic test platform according to claim 12, where Maerkl et al. teaches that each said reaction unit comprises: a first said microfluidic valve configured for providing selective fluid communication between the respective said reaction unit and the first network (valve 4406 for providing fluid communication between the horizontal channels 4402a and cell pen 4404 (reaction unit), see Fig. 18A-D and [0196] in Maerkl et al.), but does not teach a second microfluidic valve between the respective said reaction chamber and the respective said active agent chamber.
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Annotated Fig. 8D
However, the analogous art of Paliwal et al. teaches a second microfluidic valve configured for providing selective fluid communication between the respective said reaction chamber and the respective said active agent chamber (drug inlet valve places drug inlet (active agent chamber) and cell chamber (reaction chamber) in communication, see annotated Fig. 8D and [0047] in Paliwal et al).
It would have been obvious to a person possessing ordinary skill in the art before the effective filing date of the instant application to have modified the reaction unit of Maerkl et al. to include the second valve between the two chambers of the reaction unit as outlined by Paliwal et al. for the benefit of prevent back-flow between the chambers of the reaction unit (see [0047] in Paliwal et al). The modification of the reaction unit of Maerkl et al. to include the valve of Paliwal et al. would have had the reasonable expectation of successfully facilitating the flow of fluid within a cell-based assay.
Regarding claim 13, modified Maerkl et al. teaches the microfluidic test platform according to claim 2, wherein said control system comprises a plurality of microfluidic control lines, each said microfluidic control line configured for controlling operation of one or more said microfluidic valves associated with the respective said microfluidic control line (control lines control the operation of the valves of the microfluidic device, see [0173]).
Regarding claim 29, modified Maerkl et al. teaches the microfluidic test platform according to claim 1, wherein said block comprises a block member in overlying fixed relationship with a base member, and wherein said block member comprises an outer- facing first block surface and an outer-facing second block surface, wherein the second block surface is spaced from the first block surface by a block member thickness dimension (elastomeric structure 24 (block) lies on top of planar substrate 14 (base member) where the elastomeric structure 24 comprises first layer 20 and second layer 22 that are spaced by a small membrane 25 (block member thickness dimension), see Fig. 7A-B and [0083]- [0086]), and, wherein said block member comprises a first block layer (20) in overlying abutting relationship with a second block layer (22), wherein the second block layer comprises said control system (layer 22 atop layer 20 comprises expanding channel 32 used to create pumps to control fluid flow, see Fig. 7H and [0135]- [0138]), and said first block layer comprises said first plurality of reaction units, said first network and said second network (layer 20 comprises channel 30, see [0135]- [0139]) where the cell pens 4404 (reaction units) are in selective communication with horizontal channels 4402a and vertical channels 4402b via valves 4406, see Fig. 18A-D and [0196]); and
wherein the block member is manufactured with the first block layer and the first block layer and the second block layer being subsequently affixed to one another in the respective said overlying relationship (layer 22 is manufactured atop layer 20, see Fig. 7A and [0135]).
However, Maerkl et al. does not teach that the block is manufactured responsive to the active agents being provided in the respective reaction units.
Instead, in the analogous art of microfluidic devices for monitoring a reagent and sample reaction, Gong teaches a microfluidic device containing assay stations with pre-applied reagents, see [0074], where the reagent is a small molecule, see [0086].
It would have been obvious to a person possessing ordinary skill in the art before the effective filing date to have modified the cell pens of Maerkl to include the pre-applied, or pre-loaded, reagents of Gong for the benefit of pre-selecting a library of reagents that react to a cell sample for the monitoring of cell death (see [0231]- [0232] in Gong). Providing dried reagents within an assay chamber was previously known in the art as exemplified by Gong; therefore, the modification of the cell pen of Maerkl to include the pre-loaded reagent of Gong would have had the reasonable expectation of successfully facilitating the mixing of a reagent and a sample to monitor a cell sample’s viability, specifically in response to adding the reagent during the manufacture of the device.
Regarding claim 31, modified Maerkl et al. teaches the microfluidic test platform according to claim 12, wherein for each said reaction unit, each respective feeding port has a width (100 µm, see [0302]), but does not explicitly teach that each said seeding channel of each respective said group of seeding channels has a width of about 5 micron, and each respective feeding port has a width of about 20 micron.
While Maerkl does not explicitly teach that each said seeding channel of each respective said group of seeding channels has a width of about 5 micron and the feeding channels having a width of 20 microns, the invention recites that the width of the channels can be different and have a width of 0.1 µm and 20 µm, see [0100], where the modification of the channels of the microfluidic platform would allow for different fluidic operations therein.
Further, there were design incentives for implementing the claimed variation. Specifically, the modification of the seeding channels to have a dimension of 0.1 µm would have had the benefit of being applied to optical interrogation methods, and the larger width channel would have had the benefit of storing larger amounts of liquid for deposition into a cell channel, see [0102] in Maerkl et al. Therefore, as of the effective filing date of the claimed invention, the altering of the dimensions of the microfluidic channels would have been recognized as predictable to one of ordinary skill in the art.
Claims 14-15 are rejected under 35 U.S.C. 103 as being unpatentable over Maerkl et al. (US 2014/0065653) in view of Gong et al. (US 20030138941) and further in view of Paliwal et al. (US 2015/0355165 as applied to claim 12 above, and further in view of Cereda et al. (US 2019/0201897).
Regarding claim 14, modified Maerkl et al. teaches the test platform as described by claim 12, but does not teach an associated housing.
However, in the analogous art of microfluidic systems for the analysis of biological molecules, Cereda et al. teaches a system, comprising: - a housing configured for accommodating therein a microfluidic test platform (control machine 3 (housing) contains cartridge 5 (test platform) within supports 28, see Fig. 1 and [0090]); - an imaging system; - an environment control system; - a pressurization system; and - a supply system. (the control machine 3 comprises an optical detector 37 (imaging system), heating and temperature-control element 48 (environment control system), a pump 25 (pressurization system), and reagent containers 46 (supply system), see Fig. 1 and [0090]- [0094]).
It would have been obvious to a person possessing ordinary skill in the art before the effective filing date of the instant application to have modified the system of Maerkl et al. including the test platform, to include the housing of Cereda et al. for the benefit of controlling environmental parameters of the microfluidic platform to detect a target analyte and its response to the environment (see [0090] in Cereda et al.). The modification of the microfluidic device of Maerkl et al. to include the housing of Cereda et al. would have had a reasonable expectation of providing a point-of-care platform for a biological testing device.
Regarding claim 15, Maerkl et al. modified by Cereda et al. teaches the system according to claim 14, wherein: (a) said system including:
- wherein said housing defines an internal microenvironment chamber configured for accommodating the platform therein (support 28 (chamber) accommodates cartridge 2 (platform), see Fig. 1 and [0097]);
(b) said system further comprising said platform accommodated in said housing (support 28 holds cartridge 2 within control machine 3 (housing), see Fig. 1).
Claim 30 is rejected under 35 U.S.C. 103 as being unpatentable over Maerkl et al. (US 2014/0065653) in view of Gong et al. (US 20030138941) and in view of Paliwal et al. (US 2015/0355165) as applied to claim 12 above, and further in view of Isakova et al. (US 20190091689).
Regarding claim 30, modified Maerkl teaches the microfluidic test platform according to claim 12, wherein the active agent chamber is in selective fluid communication with the reaction chamber (drug inlet valve places drug inlet (active agent chamber) and cell chamber (reaction chamber) in communication, see annotated Fig. 8D and [0047] in Paliwal et al), but does not teach that the active agent chamber is exclusively in selective fluid communication with the reaction chamber.
However, in the analogous art of microfluidic devices for monitoring cell reactions to nucleic acid sequences, Isakova et al. teaches a spotting chamber 7 directly connected to cell trapping pen 2, see Fig. 1B and [0035]. It would have been obvious to a person possessing ordinary skill in the art before the effective filing date of the instant application to have modified the microfluidic device of previous modified Maerkl to include the chamber exclusively connected to a reaction chamber as exemplified by Isakova et al. for the benefit of providing the input of different drug directly to each reaction chamber to monitor a cell’s reaction to each specific drug sequence (see [0035] in Isakova).
A person possessing ordinary skill in the art would have been motivated to modify the drug inlet of previously modified Maerkl to be exclusively connected to the reaction chamber as exemplified by Isakova et al. for the benefit of providing the input of different drug directly to each reaction chamber to monitor a cell’s reaction to each specific drug sequence (see [0035] in Isakova). The modification of the modified device of Maerkl to include the direct connection of Isakova would have yielded the reasonable expectation of successfully facilitating the input of different drugs for the reaction between a drug active agent and cell for a cell-based assay.
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.
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/A.N.M./ Examiner, Art Unit 1758
/SAMUEL P SIEFKE/Primary Examiner, Art Unit 1758