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 .
Response to Arguments
Applicant’s arguments, see Remarks page 8, filed 16 June 2026, with respect to the rejections of claims 1, 2, 6, 9, 11, 18, 20, and 24 under 35 U.S.C 103 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn.
The examiner appreciates the applicant’s arguments that “a sensing system including a photonic integrated circuit,” such as that taught by Reumers et al, is not equivalent to “a photonic integrated circuit sensor.” Likewise, the language of “functionalized” is narrower than that of “functional to.”
Upon consideration of applicant’s arguments, the examiner believes that the previous grounds of rejection amounted to “a device with a sensing system including a photonic integrated circuit which is functional to detect an analyte.” However, this is broader than applicant’s claimed “a first photonic integrated circuit sensor […], which first PIC sensor is functionalized to detect the presence of a first analyte…”
A new grounds of rejection is made in view of Estevez et al (Estevez M, Alvarez M, Lechuga M. “Integrated Optical Devices for Lab-On-A-Chip Biosensing Applications.” Laser Photonics Rev. 6., No 4., 463 – 487, cited on the IDS filed 29 April 2023) in a second non-final action.
Status of Claims
Applicant's amendments to the claims filed 16 June 2026 have been entered. Applicant's remarks filed 16 June 2026 are acknowledged.
Claims 1, 2, 6, 9, 11, 18, 20, and 24 are in status “Original” or “Previously presented.” Claims 75 – 78 are new. Claims 28, 29, 33, 35, 54, 55, 56, 59, 60,62, 66 – 68, 71, and 73 are withdrawn as non-elected subject matter. Claims 3 – 5, 7, 8, 10, 12 – 17, 19, 21 – 23, 25 – 27, 30 – 32, 34, 36 – 53, 57, 58, 61, 63 – 65, 69, 70, 72, and 74 are canceled.
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, 2, 9, 11, 18, 20, 24, 75, 76, and 78 are rejected under 35 U.S.C. 103 as being unpatentable over Noh et al (US 20130236972 A1) in view of McCarthy et al (US 20160089673 A1, provided on the 892 submitted 04 December 2025) and further in view of Estevez et al (Estevez M, Alvarez M, Lechuga M. “Integrated Optical Devices for Lab-On-A-Chip Biosensing Applications.” Laser Photonics Rev. 6., No 4., 463 – 487, cited on the IDS filed 29 April 2023).
With regards to claim 1, Noh et al teaches;
The claimed “A microfluidic device” has been read on the taught ([0013], “Liver sinusoid model 100 is an in vitro microfluidic model…”);
The claimed “a first microchannel fluidly connected to a port on an exterior of said device, and having a length, a first end, and a second end” has been read on the taught ([0014], “Top microchannel 112 also includes a top inlet passage 115 at a first end 112a of top microchannel 112 and a top outlet passage 116 and a second end 112b of top microchannel 112.”);
The claimed “an ultrathin membrane having nanopores, mesopores, micropores, or a combination of two or more of these, said ultrathin membrane having a first side and a second side, wherein said first side of said membrane is fluidly connected through said first microchannel to said port on said exterior of said device” and “a second microfluidic channel, which second microfluidic channel faces said ultrathin membrane and is fluidly connected to receive any fluid coming through nanopores, mesopores, micropores, or combinations thereof of said ultrathin membrane” have been read on the taught ([0015], “A microporous membrane 120 is placed over the top of bottom substrate 106 so that membrane 120 covers microchannel 114. […] It is desired that the pores are sufficiently large enough to allow liquids and proteins to pass through from one side of membrane 120 to opposing side of membrane 120… second microchannel 114 is generally parallel to first microchannel 112, with microchannels 112, 114 being separated from each other by membrane 120.”; Bottom microchannel 114 reads on a second microfluidic channel.);
However, Noh et al does not explicitly disclose wherein a sensor is integrated into the microfluidic device including ultrathin membranes.
In the analogous art of microfluidic cell culture devices, McCarthy et al teaches;
The claimed “a microfluidic device” has been read on the taught ([0055], “…self-contained microfluidic drive module 24 for the single cell flexing device 2 that would provide actuation for one single well 8 in the baseplate 12.”; A microfluidic drive module for the device reads on a microfluidic device);
“Two channels separated by an ultrathin porous membrane” has been read on the taught ([0066], “The flexible membrane 34 is cut to fit within an upper recess 92 in the upper structure 94 of the flexing chamber 6. The flexible membrane 34 (silicone or other flexible material, including tissue specific cell matrix components,) would be preferably either a solid surface or perforated with micropores (between 5-30 μm), the latter membrane 34 could be used in studies requiring co-culture of cells above and below the plane of the silicone membrane 34, with cells below the plane of silicone in a lower recess 96 in the lower structure 98.”; Upper structure 94 reads on a first channel. Lower structure 98 reads on a second channel. Flexible membrane 34 which is perforated with micropores reads on an ultrathin porous membrane).
“A sensing device disposed in said first microchannel or in said second microchannel, which said sensor is functionalized to detect the presence of a first analyte of interest in fluid in said first microchannel or said second microchannel, respectively” has been read on the taught ([0081], “..a microwell plate 130 format flexing chamber 6 that facilitates imaging of cell response to stretch using an upright microscope format… An optional addition to the flexing chamber 6 would permit the placement within one well 8 from each row of a pressure/strain or other sensor to provide real-time readout to the host computer 38 of the mechanical strain occurring during the flex cycle for each row.”; Permitting the imaging of a cell response supports a device which can be combined with optical methods. A sensor to provide real-time readout supports a device which allows sensors to be disposed within the microchannel.).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the microfluidic device as taught by Noh et al with the sensing components as taught by McCarthy et al, for the predictable benefit of allowing direct, in-vivo data collection of cell responses to the conditions within the microfluidic device (McCarthy et al, [0009], “This allows for the direct in vivo imaging of biosensor activation in response to a single displacement force.”).
However, Noh et al in view of McCarthy et al does not explicitly disclose wherein the sensor is a photonic integrated sensor.
In the analogous art of cell sensing methods, Estevez et al teaches;
The claimed “a first photonic integrated circuit sensor […] functionalized to detect the presence of a first analyte of interest in fluid” has been read on the taught (Page 472, paragraph 4, “Recently, the same group has reported an array of SOI microring resonators […] A PDMS flow cell with independent microfluidic channels (200 × 50 μm2) was mounted on top of the chip for sample delivery. The multiplexed capabilities were evaluated by immobilizing three different proteins and by successively flowing two of the three specific antibodies.”; An array of microring resonators reads on a first photonic integrated circuit. Immobilizing proteins reads on functionalization. A flow cell with microfluidic channels reads on the detection of analyte in fluid.).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the cell culturing device which allows for sensing as taught by Noh et al in view of McCarthy et al with the photonic integrated circuit as taught by Estevez et al, for the predictable benefit of allowing sensitive, label-free, real-time detection of analytes (Estevez et al, page 463, paragraph 3, “Photonic biosensors are well-established technologies for the sensitive monitoring of molecular interactions. They could afford the requirements for the “on-chip” detection in lab-on-a-chip platforms due to their outstanding characteristics of sensitivity, label-free and real-time detection.”).
With regards to claim 2, the device of claim 1 is obvious over Noh et al in view of McCarthy et al and further in view of Estevez et al.
Noh et al additionally teaches;
The claimed “wherein said ultrathin membrane is a nanoporous membrane, a mesoporous, a microporous membrane, has a combination of any two pore sizes selected from nanopores, mesopores, and micropores, or has nanopores, mesopores, and micropores” has been read on the taught ([0015], “A microporous membrane 120 is placed over the top of bottom substrate 106 so that membrane 120 covers microchannel 114.”).
With regards to claim 9, the device of claim 1 is obvious over Noh et al in view of McCarthy et al and further in view of Estevez et al.
The limitation of “a second PIC sensor, which second PIC sensor is disposed in said first microchannel or in said second microchannel, and is functionalized to detect the presence of a second analyte of interest in fluid in said first microchannel or said second microchannel, respectively” is drawn exclusively to the duplication of parts.
According to MPEP 2144.04(VI)(B), “mere duplication of parts has no patentable significance unless a new and unexpected result is produced.”—see In reHarza, 274 F.2d 669, 124 USPQ 378 (CCPA 1960). Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the microfluidic device including a PIC sensor as taught by Noh et al in view of NAME and further in view of NAME with a second PIC sensor, for the predictable advantages of allowing quality control redundancy or the concurrent measurement of a second analyte.
With regards to claim 11, the device of claim 1 is obvious over Noh et al in view of McCarthy et al and further in view of Estevez et al.
Noh et al additionally teaches;
The claimed “an outlet in said second microchannel to allow fluids in said second microchannel to exit the device” has been read on the taught ([0015], “Bottom microchannel 112 also includes […] a bottom outlet passage 118 at a second end 114b of bottom microchannel 114.”).
With regards to claim 18, the device of claim 1 is obvious over Noh et al in view of McCarthy et al and further in view of Estevez et al.
The limitation of a device “configured to allow said first PIC sensor to be exchanged by sliding said first PIC sensor out and sliding a fresh PIC sensor in” is drawn exclusively to making parts separable.
According to MPEP 2144.04(V)(C), making parts separable is prima facie obvious, provided that is desirable for any reason to access the part; see In reDulberg, 289 F.2d 522, 523, 129 USPQ 348, 349 (CCPA 1961). In the case of the instant invention, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device with a separable PIC sensor, for the predictable advantage of allowing broken sensor components to be replaced.
With regards to claim 20, the device of claim 1 is obvious over Noh et al in view of McCarthy et al and further in view of Estevez et al.
Noh et al additionally teaches;
The claimed “wherein cells of a first type are disposed on said first side of said ultrathin membrane” has been read on the taught ([0016], “A plurality of liver cells 130 are disposed on membrane 120 in first microchannel 112.”; See also figure 10.).
With regards to claim 24, the device of claim 20 is obvious over Noh et al in view of McCarthy et al and further in view of Estevez et al.
The limitation “wherein said cells of a first cell type disposed on said first side of said ultrathin membrane are tendon fibroblasts” and “configured to provide uniaxial stress to said tendon fibroblasts describe the material being worked upon by the apparatus. The positively recited structural limitations are met by Noh et al in view of McCarthy et al and further in view of Estevez et al. As discussed in the rejection of claim 20, the device of Noh et al is suitable for culturing cells. No expressed or implied structure is added by the specified “tendon fibroblasts.” Accordingly, this limitation does not render claim 24 patentably distinct over the combination of Noh et al in view of McCarthy et al and further in view of Estevez et al; Please see MPEP 2115.
However, neither Noh et al nor Estevez et al address the limitation wherein “said device is configured to provide uniaxial stress…”
McCarthy et al further teaches;
The claimed “wherein said device is configured to provide uniaxial stress” has been read on the taught (Abstract, “A hydraulic cell stretching device comprising a source of variable pressured hydraulic fluid hydraulically coupled to a flexing chamber.”; [0006], “Once attached to the flexible substratum, the cells can be subjected to cyclic stretching in either direction (e.g., positive or negative stretch)…”; Stretching reads on providing uniaxial stress to cultured cells.)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device of Noh et al in view of McCarthy et al in view of Estevez et al with the hydraulic membrane stretching as taught by McCarthy et al, for the benefit of creating a device which allows cellular response to stress to be tested (McCarthy et al, [0084], “At face value, the disclosed device 2 could be used for exploring basic research questions with regard to the effects of cyclic stretch of cells (similar to what occurs in vivo in blood vessels).”).
With regards to claim 75, the device of claim 1 is obvious over Noh et al in view of McCarthy et al and further in view of Estevez et al.
Neither Noh et al nor McCarthy et al explicitly disclose wherein the first PIC sensor comprises a photonic ring resonator, a photonic crystal, a spiral wave guide, or a Mach-Zehnder interferometer.
Estevez et al further teaches;
The claimed “wherein the first PIC sensor comprises a photonic ring resonator, a photonic crystal, a spiral wave guide, or a Mach-Zehnder interferometer” has been read on the taught (Page 472, paragraph 4, “Recently, the same group has reported an array of SOI microring resonators…”; Microring resonators read on a photonic ring resonator.).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the cell culturing device which allows for sensing as taught by Noh et al in view of McCarthy et al with the photonic ring resonator as taught by Estevez et al, for the predictable benefit of allowing sensitive, label-free, real-time detection of analytes (Estevez et al, page 463, paragraph 3, “Photonic biosensors are well-established technologies for the sensitive monitoring of molecular interactions. They could afford the requirements for the “on-chip” detection in lab-on-a-chip platforms due to their outstanding characteristics of sensitivity, label-free and real-time detection.”).
With regards to claim 76, the device of claim 1 is obvious over Noh et al in view of McCarthy et al and further in view of Estevez et al.
Neither Noh et al nor McCarthy et al explicitly disclose wherein the first PIC sensor is covalently bound to an antibody that specifically binds the first analyte.
Estevez et al additionally teaches;
The claimed “wherein the first PIC sensor is covalently bound to an antibody that specifically binds the first analyte” has been read on the taught (Page 465, Figure 2 caption, “Mixed self-assembled monolayer (SAM) with reactive and non-reactive silanes compounds with specific antibodies covalently immobilized for protein recognition…” Covalently immobilized antibodies read on covalently bound antibodies that specifically bind to the first analyte.).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the cell culturing device which allows for sensing as taught by Noh et al in view of McCarthy et al with the photonic integrated circuit as taught by Estevez et al, for the predictable benefit of allowing sensitive, label-free, real-time detection of analytes (Estevez et al, page 463, paragraph 3, “Photonic biosensors are well-established technologies for the sensitive monitoring of molecular interactions. They could afford the requirements for the “on-chip” detection in lab-on-a-chip platforms due to their outstanding characteristics of sensitivity, label-free and real-time detection.”).
With regards to claim 78, the device of claim 1 is obvious over Noh et al in view of McCarthy et al and further in view of Estevez et al.
Neither Noh et al nor Estevez et al explicitly disclose wherein the ultrathin membrane comprises silicon, silicon nitride, silicon oxide, or silicon dioxide.
McCarthy et al additionally teaches;
The claimed “wherein the ultrathin membrane comprises silicon” has been read on the taught ([0006], “The first embodiment of this device consists of a 3 well unit, each well having a flexible silicon membrane…”; A silicon membrane reads on the ultrathin membrane comprising silicon.).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device of Noh et al in view of McCarthy et al in view of Estevez et al with the silicon membrane as taught by McCarthy et al, for the predictable benefit of allowing the membrane to be easily derivatizable for cell adhesion (McCarthy et al, [0010], “Fourth, the substrate is easily derivatizable silicon, which permits coupling a wide range of ligands to the substratum for cell adhesion.”).
Claims 6 and 77 are rejected under 35 U.S.C. 103 as being unpatentable over Noh et al (US 20130236972 A1) in view of McCarthy et al (US 20160089673 A1) in view Estevez et al (Estevez M, Alvarez M, Lechuga M. “Integrated Optical Devices for Lab-On-A-Chip Biosensing Applications.” Laser Photonics Rev. 6., No 4., 463 – 487, cited on the IDS filed 29 April 2023) as applied to claim 1 above, and further in view of DesOrmeaux et al (DesOrmeaux, et al., "Nanoporous silicon nitride membranes fabricated from porous nanocrystalline silicon templates", Nanoscale, 2014. 6(18): p. 10798-10805; Cited on the IDS provided 30 January 2026).
With regards to claim 6, the device of claim 1 is obvious over Noh et al in view of McCarthy et al and further in view of Estevez et al.
However, this combination does not explicitly disclose wherein the ultrathin membrane is of silicon nitride.
In the analogous art of ultrathin membranes, DesOrmeaux et al teaches;
The claimed “wherein said ultrathin membrane is of silicon nitride” has been read on the taught (Abstract, “Here we present a facile, wafer-scale method to produce nanoporous silicon nitride (NPN) membranes…”; Page 2 paragraph 2, “The mechanical strength of SiN has enabled free-standing thin films including microporous and nanoporous membranes.”).
It would have been obvious to one of ordinary skill in the art to modify the device of Noh et al in view of McCarthy et al and further in view of Estevez et al with the ultrathin membrane made of silicon nitride as taught by DesOrmeaux et al, for the predictable benefit of enabling excellent flow through a stronger and more chemically stable membrane (DesOrmeaux, Page 10799 paragraph 4, “NPN membranes share the excellent flow and separation characteristics of pnc-Si while being markedly stronger and more chemically stable.”).
With regards to claim 77, the device of claim 1 is obvious over Noh et al in view of McCarthy et al and further in view of Estevez et al.
However, this combination does not explicitly disclose wherein the ultrathin membrane has a thickness less than 400 nm.
In the analogous art of ultrathin membranes, DesOrmeaux et al teaches;
The claimed “wherein the ultrathin membrane has a thickness less than 400 nm” has been read on the taught (Page 10804, “The resulting structure was a 40 nm pnc-Si hard mask above a solid 50 nm SiN film on the bulk silicon surface… Finally, a 10 : 1 BOE immersion removes the remaining SiO2 and the freestanding NPN films are revealed.”; A 50nm SiN film reads on a membrane having a thickness less than 400nm).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device including an ultrathin membrane as taught by Noh et al in view of McCarthy et al and further in view of Estevez et al, with the membrane having a thickness less than 400 nm, as taught by DesOrmeaux et al. Per MPEP 2143(I)(B), simple substitution of one known element for another to obtain predictable results may be prima facie obvious. In the case of the instant invention, the prior art of Noh et al in view of McCarthy et al and further in view of Estevez et al contains a device which differs from the claimed device by substitution of a generic membrane with an ultrathin membrane with a thickness less than 400nm. The substituted component of an ultrathin membrane with a thickness less than 400nm is known in the art of DesOrmeaux et al. One of ordinary skill in the art could have substituted one known element for another, for the predictable result of creating a device with a porous, thin membrane with a controlled porosity, stretch, and flow speed.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALISON CLAIRE GERHARD whose telephone number is (571)270-0945. The examiner can normally be reached M-F, 9:00 - 5:30pm EST.
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/ALISON CLAIRE GERHARD/Examiner, Art Unit 1797 /LYLE ALEXANDER/Supervisory Patent Examiner, Art Unit 1797
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