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 .
Response to Amendment
Applicant amendments filed 12/03/2025 have been entered.
Status of Claims
Claims 1, 3, 5-9, 29-35 remain pending in the application.
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.
Claim(s) 1, 3, 5-7, 29-33 is/are rejected under 35 U.S.C. 103 as being unpatentable over Cha (US-2017/0211029-A1) in view of Wang (US-2019/0161715-A1).
Regarding claim 1, Cha teaches a microfluidic device (neurovascular unit (NVU)-on-a-chip 100) with spatially controlled cell isolation capacity ([0062], Figure 1), comprising:
a body (substrate 10) having ([0061], [0062], Figure 1):
a chamber (cell fixing well 20) within the body (10), the chamber (20) defined by first and second sides, first and second ends, and a lower interior surface ([0064], Figure 1); and
It is described that the cell fixing well 20 (chamber) has a first side wall WS1 and a second side wall WS2, where it is further seen in Figure 1 that the cell fixing well 20 (chamber) has the side walls, and first and second ends ([0064]). In the annotated Figure 1 below, the dashed rectangle encloses a first end of the cell fixing well 20, where the side opposite to the dashed rectangle is a second end. The solid rectangle encloses a first side, where the side opposite to the solid rectangle is a second side. Cha further describes in [0080] the formation of channel 75, where an ECM material fills the cell fixing well 20 and [0087] then describes where the ECM simulation material 70 can be put into a gel state by applying heat such that the micro-needle 60 can be removed. Therefore there would need to be a lower surface that defines the cell fixing well 20 such that the ECM simulation material 70 does not fall out the bottom.
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first and second gradient ports communicating with the chamber (20), the first gradient port adjacent to the first side of the chamber (20) and the second gradient port adjacent the second side of the chamber (20);
Figures 3-9 show the method of fabricating the NVU-on-a-chip 100 (microfluidic device), where there is a first passage 35 and second passage 45 that each have an inlet port IP and outlet port OP ([0080], [0084], Figure 3). The two outlet ports labeled in Figure 3 are the first and second gradient ports that communicate with the cell fixing well 20 (chamber), where one of the outlet ports is adjacent to the first side of cell fixing well 20 and the other outlet port is adjacent to the second side of the cell fixing well 20. The outlet ports have been labeled in annotated Figure 1 supra for clarity.
a hydrogel polymerized in the chamber (20), the hydrogel defining a passageway (channel 75) extending along a first axis from the first gradient port and the second gradient port ([0075], Figure 1);
[0080] describes potential materials for the ECM simulation material, that includes a hydrogel. The passageway will be the channel 75 that extends along a first axis from the two outlet ports (first and second gradient ports), please see annotated Figure 1 below which points directly to the channel 75 being mapped to “the passageway” for further clarity.
a moveable rod (micro-needle 60) positionable in the passageway (75) and having a first end supportable by the first gradient port and a second end supportable by the second gradient port ([0084], Figure 4); and
It is seen in Figure 4 that there are micro-needles 60 that can pass through the first passage 35 in a first direction D1 to be inserted into the second passage 45 via cell fixing well 20 ([0084]). It is further seen in Figure 4 that the micro-needles 60 (movable rod) will be supported by the two outlet ports (first and second gradient ports) that were labeled in Figure 3.
Cha does not teach a body having:
an upper surface;
an upper interior surface;
a first loading port communicating with the chamber at a location adjacent the first end of the chamber;
a second loading port communicating with the chamber at a location adjacent the second end of the chamber, the first and second loading ports lying along a loading axis; and
a first plurality of diffusion ports extending through the body between the upper surface of the body and the upper interior surface of the body, the first plurality of diffusion ports communicating with the hydrogel in the chamber at a location laterally spaced from the passageway, and being axially spaced along a second axis parallel to the first axis and extending through the first and second sides of the chamber;
wherein:
at least a portion of the body between into the upper surface of the body and the upper interior surface of the body is gas permeable;
the first plurality of diffusion ports communicate with an environment external of the body;
the hydrogel separates and is positioned between the first and second loading ports and the passageway such that the first and second loading ports are out of direct communication with the passageway;
the first plurality of diffusion ports are configured such that a first media deposited on the first plurality of diffusion ports diffuse into the hydrogel and forms a gradient of the first media in the hydrogel from the first end of the chamber to the second end of the chamber; and
the loading axis being non-parallel to the first axis.
In the analogous art of three dimensional microfluidic cell arrays or microfluidic tissue arrays that functions as a scaffold for growing cells or tissues, Wang teaches a layered microfluidic array (Wang; [0003], [0007]).
Specifically, Wang teaches a microfluidic living cell array 100 that comprises a first layer 101, a second layer 102, and a third layer 103 that are stacked together into a single cell array 100 (Wang; [0026], Figure 1). In the first layer there are a plurality of cell culture channels 104 that includes a plurality of cell culture chambers 122, the third layer 103 comprises a membrane 110 with a nest of pores 112 that fluidly connect a cell culture channel to a microfluidic channel 108 of the second layer 102 (Wang; [0026], Figure 1). [0028] of Wang describes that during operation, cells are introduced into the cell culture channels 104, where the channels 104 may be filled with a hydrogel media that provides a porous environment suitable for growing cells. Nutrients are dissolved or suspended in a liquid and are introduced into the fluid inlet 114 at a predetermined rate and flows through the microfluidic channel 108 until it exits at the fluid outlet 118 (Wang; [0028]). It is further described by [0029] of Wang that the nest of pores 112 fluidly connect the microfluidic channel 108 to the cell culture channels 104, where nutrients pass into the cell culture channels 104 in the direction of arrow 202 seen in Figure 2 of Wang, where the nutrients are limited by the size of the pores. It is seen in Figure 7 of Wang that the first layer can instead be first layer 701 that has a plurality of cell culture channels 704 that do not include designated cell culture chambers 122 such that cellular growth occurs within cell culture channels 704 (Wang; [0036]). It is understood that there would still be nests of pores 112 that are above the cell culture channels 704 along with a second layer 102 with microfluidic channels 108 above it.
It is seen in Figure 1 of Wang that there is a fluid inlet 114 that will be connected to a syringe pump for delivering fluids at a predetermined flow rate (Wang; [0027]). It is further described by [0041] of Wang that fluid inlets and outlets are exchangeable, which permits a number of drugs to be introduced. As example, there can be two inlets with eight outlets, or eight inlets with two outlets, where “The fluid inlets and fluid outlets are not necessarily at opposite ends of the cell array. Depending on the fluid pathway, the fluid inlet and/or fluid outlet may be positioned at another location.” (Wang; [0041]). It is specifically seen in Figure 4 of Wang where there are two inlets 414 that are understood to be holes in the surface of layer 402, which would be similar to how the outlets 118 in Figure 1 are shown.
It would have been obvious to one skilled in the art to modify the neurovascular unit-on-a-chip of Cha such that it includes the layer with the nest of pores and the corresponding layer with inlets that delivers fluid to the nest of pores as taught by Wang because Wang teaches that the pores provides a diffusion-controlled process, as nutrients in the fluid that pass into the cell culture channels are limited by the size of the pores (Wang; [0029]).
Layers 102 and 103 of Wang will now be placed on top of the substrate 10 of Cha, where each of the rows of pores will align with each of the channels 75. The underside of layer 103 of Wang is the upper interior surface, and the outer surface of layer 103 is the upper surface. Therefore, the nests of pores will extend through the body between the upper surface of the body and the upper interior surface of the body.
In the annotated Figure 1 below, it has been indicated which channel 75 is being considered the passageway, along with a dashed box that encloses a channel 75 where a first row of nests of pores will be located and a second solid box that encloses a channel 75 that a second row of nests of pores will be located. From the annotated Figure 1 below, the first group of nests of pores will be a first plurality of diffusion ports that extend between layer 103 of Wang at a location laterally spaced from the channel 75 (passageway as annotated below), where the first group of nests of pores will be axially spaced along a second axis that is parallel to the first axis (axis along which channel 75 as annotated is located, a dashed line has been added that represents the first axis) extending through first and second sides of the chamber (please see the annotated Figure 1 above which indicates the sides and ends of the cell fixing well 20). The nests of pores of Wang will communicate with the ECM simulation material in the cell fixing well 20 (chamber) of Cha.
Further, there will be an inlet associated with a location of each of the channels 75 of Cha. As such, there will be an inlet port associated with the first group of nest pores (first loading port adjacent the first end of the chamber) and an inlet port associated with the second group of nest pores (second loading port adjacent the second end of the chamber). These inlets lay along a loading axis, which has been added to annotated Figure 1 below. Further, as seen in the annotated Figure 1 below, the ECM material (hydrogel) will be between the first and second inlet ports associated with the first and second group of nest pores and the annotated passageway seen below such that the inlet ports and passageway are out of direct communication. Additionally, the loading axis is non-parallel to the first axis.
The nests of pores communicate with the inlet port described above, where the inlet port communicates with an environment external of the body.
As described by [0039] of Wang, the first, second, and third layers are made of a material such as PDMS. While Wang does not address gas permeability, it has been determined that where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In the current case, obviousness. Absent persuasive evidence that the PDMS materials are different, the prior art is considered to have the same properties with respect to gas permeability as that is claimed. MPEP § 2112.01 (I-IV).
Further, please see page 7 lines 10-12 and page 11 lines 27-28 of the instant specification which state that PDMS is a gas permeable material.
The limitation “the first plurality of diffusion ports are configured such that a first media deposited on the first plurality of diffusion ports diffuse into the hydrogel and forms a gradient of the first media in the hydrogel from the first end of the chamber to the second end of the chamber” is directed to the function of the apparatus and/or the manner of operating the apparatus, all the structural limitations of the claim has been disclosed by modified Cha and the apparatus of modified Cha is capable of depositing a first media on the first plurality of diffusion ports to form a gradient. As such, it is deemed that the claimed apparatus is not differentiated from the apparatus of modified Cha (see MPEP §2114).
Further, the first media is not positively recited in the claims, and is therefore not a part of the microfluidic device.
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Regarding claim 3, modified Cha teaches the microfluidic device of claim 1. Modified Cha further teaches a second plurality of diffusion ports extending into the upper surface of the body and communicating with the chamber, the second plurality of diffusion ports axially spaced along an axis extending though the first and second sides of the chamber and parallel to the second axis along which the first plurality of diffusion ports is axially spaced.
Layers 102 and 103 of Wang are placed on top of substrate 10 of Cha such that each of the rows of nests of pores will align with each of the three channels 75, where each channel 75 will have its own group of nests of pores and where the outer surface of layer 103 of Wang will form the upper surface. From the annotated Figure 1 supra, it details which channel 75 is being considered the passageway where in the solid rectangle box encloses the location of the second group of nests of pores. This second group of nests of pores is a second plurality of diffusion ports that similarly extend into 103 (upper surface) and communicate with cell fixing well 20 (chamber), where the second group of nests of pores are axially spaced along an axis extending through first and second sides of cell fixing well 20 (chamber) and are parallel to the second axis along which the first group of nests of pores is.
Regarding claim 5, modified Cha teaches the microfluidic device of claim 1. Cha further teaches wherein the rod is movable between a first position wherein the rod is within the passageway in the hydrogel and a second position wherein the rod is removed from the hydrogel.
[0080] of Cha describes how channel 75 (see Figure 7) passing through ECM simulation material 70 is formed, where the ECM material includes “an extracellular matrix including at least one of collagen, fibronectin, fibrin, fibrinogen, elastin, hyaluronic acid, proteoglycan, laminin, heparin sulfate, chondroitin sulfate, keratin sulfate and Matrigel, hydrogel including at least one of alginate, polyethylene glycol, silicon hydrogel, polyacrylamide, polyethylene oxide, polypyrrolidone, glycosaminoglycan and polyhema, mixture of the extracellular matrix and hydrogel, chemical variant of the extracellular matrix, chemical variant of the hydrogel, or mixture of the chemical variant of the extracellular matrix and the chemical variant of the hydrogel.” [0084] of Cha describes where the forming of the channel 75 includes inserting micro-needle 60 into the first passage 35, cell fixing well 20, and the second passage 45, and then filling the cell fixing well 20 with an ECM simulation material in a sol state, where [0085] describes where the ECM simulation material in the sol state is formed along the micro-needle 60 in the cell fixing well 20 to cover and surround the micro-needle 60. [0087] of Cha then describes where the ECM simulation material 70 in the gel state may be formed by applying heat, where the micro-needle 60 then goes in a second direction D2 to be separated from the first passage 35 (see Figure 6 of Cha). Therefore, Figures 4 and 5 of Cha shows the micro-needle 60 (rod) in a first position where in Figure 5 of Cha it shows the micro-needle 60 (rod) in the ECM simulation material 70. Then in Figure 6 of Cha shows the micro-needle 60 (rod) being removed from the ECM simulation material 70. Figure 7 of Cha shows where the micro-needle 60 (rod) is fully removed, a second position.
Regarding claim 6, modified Cha teaches the microfluidic device of claim 1. Cha further teaches wherein the passageway is generally tubular.
It is seen in in Figure 4 of Cha that micro-needle 60 is inserted into the first passage 35 and second passage 45, where the micro-needles 60 are cylindrical, where Figure 2 of Cha shows a cross-sectional view of an extra-cellular matrix simulation material taken in region A (which is seen in Figure 1 of Cha). The cross section in Figure 2A is cylindrical. Therefore, the channel 75 will be generally tubular.
Regarding claim 7, modified Cha teaches the microfluidic device of claim 1. Cha further teaches wherein the passageway extends between the first and second sides of the chamber, the first axis of the passageway being closer to the first end of the chamber than the second end of the chamber.
The channel 75 that is being considered the passageway has been annotated in Figure 1 supra, where it is seen that the channel 75 (passageway) will extend along an axis (see annotated Figure 1 supra where the first axis has been added) between the first and second sides of the cell fixing well 20 (chamber) (see the annotated Figure 1 in relation to what is being considered sides versus ends), where the axis of the channel 75 (passageway) is closer to the first end of the cell fixing well 20 (chamber) than the second end of the cell fixing well 20 (chamber).
Regarding claim 29, Cha teaches a microfluidic device (neurovascular unit (NVU)-on-a-chip 100) with spatially controlled cell isolation capacity ([0062], Figure 1),
a body (substrate 10) having ([0061], [0062], Figure 1):
a chamber (cell fixing well 20) within the body (10), the chamber (20) defined by first and second sides, first and second ends, and a lower interior surface ([0064], Figure 1); and
It is described that the cell fixing well 20 (chamber) has a first side wall WS1 and a second side wall WS2, where it is further seen in Figure 1 that the cell fixing well 20 (chamber) has the side walls, and first and second ends ([0064]). In the annotated Figure 1 supra, the dashed rectangle encloses a first end of the cell fixing well 20, where the side opposite to the dashed rectangle is a second end. The solid rectangle encloses a first side, where the side opposite to the solid rectangle is a second side. Cha further describes in [0080] the formation of channel 75, where an ECM material fills the cell fixing well 20 and [0087] then describes where the ECM simulation material 70 can be put into a gel state by applying heat such that the micro-needle 60 can be removed. Therefore there would need to be a lower surface that defines the cell fixing well 20 such that the ECM simulation material 70 does not fall out the bottom.
first and second gradient ports communicating with the chamber (20), the first gradient port adjacent to the first side of the chamber (20) and the second gradient port adjacent the second side of the chamber (20);
Figures 3-9 show the method of fabricating the NVU-on-a-chip 100 (microfluidic device), where there is a first passage 35 and second passage 45 that each have an inlet port IP and outlet port OP ([0080], [0084], Figure 3). The two outlet ports labeled in Figure 3 are the first and second gradient ports that communicate with the cell fixing well 20 (chamber), where one of the outlet ports is adjacent to the first side of cell fixing well 20 and the other outlet port is adjacent to the second side of the cell fixing well 20. The outlet ports have been labeled in the first annotated Figure 1 supra that shows what is being considered the sides and ends.
a hydrogel polymerized in the chamber (20), the hydrogel defining a passageway (channel 75) extending along a first axis from the first gradient port and the second gradient port ([0075], Figure 1);
[0080] describes potential materials for the ECM simulation material, that includes a hydrogel. The passageway will be the channel 75 that extends along a first axis from the two outlet ports (first and second gradient ports), please see annotated Figure 1 supra which points directly to the channel 75 being mapped to “the passageway” for further clarity.
a moveable rod (micro-needle 60) positionable in the passageway (75) and having a first end supportable by the first gradient port and a second end supportable by the second gradient port ([0084], Figure 4); and
It is seen in Figure 4 that there are micro-needles 60 that can pass through the first passage 35 in a first direction D1 to be inserted into the second passage 45 via cell fixing well 20 ([0084]). It is further seen in Figure 4 that the micro-needles 60 (movable rod) will be supported by the two outlet ports (first and second gradient ports) that were labeled in Figure 3.
Cha does not teach a body having:
an upper surface;
an upper interior surface;
a first loading port communicating with the chamber at a location adjacent the first end of the chamber;
a second loading port communicating with the chamber at a location adjacent the second end of the chamber, the first and second loading ports lying along a loading axis; and
a first plurality of diffusion ports extending through the body between the upper surface of the body and the upper interior surface of the body, the first plurality of diffusion ports communicating with the hydrogel in the chamber at a location laterally spaced from the passageway, and being axially spaced along a second axis laterally spaced from the first axis and extending through the first and second sides of the chamber;
wherein:
at least a portion of the body between into the upper surface of the body and the upper interior surface of the body is gas permeable;
the first plurality of diffusion ports communicate with an environment external of the body;
the hydrogel separates and is positioned between the first and second loading ports and the passageway such that the first and second loading ports are out of direct communication with the passageway; and
the first plurality of diffusion ports are configured such that a first media deposited on the first plurality of diffusion ports diffuse into the hydrogel and forms a gradient of the first media in the hydrogel from the first end of the chamber to the second end of the chamber.
In the analogous art of three dimensional microfluidic cell arrays or microfluidic tissue arrays that functions as a scaffold for growing cells or tissues, Wang teaches a layered microfluidic array (Wang; [0003], [0007]).
Specifically, Wang teaches a microfluidic living cell array 100 that comprises a first layer 101, a second layer 102, and a third layer 103 that are stacked together into a single cell array 100 (Wang; [0026], Figure 1). In the first layer there are a plurality of cell culture channels 104 that includes a plurality of cell culture chambers 122, the third layer 103 comprises a membrane 110 with a nest of pores 112 that fluidly connect a cell culture channel to a microfluidic channel 108 of the second layer 102 (Wang; [0026], Figure 1). [0028] of Wang describes that during operation, cells are introduced into the cell culture channels 104, where the channels 104 may be filled with a hydrogel media that provides a porous environment suitable for growing cells (Wang; [0028]). Nutrients are dissolved or suspended in a liquid and are introduced into the fluid inlet 114 at a predetermined rate and flows through the microfluidic channel 108 until it exits at the fluid outlet 118 (Wang; [0028]). It is further described by [0029] of Wang that the nest of pores 112 fluidly connect the microfluidic channel 108 to the cell culture channels 104, where nutrients pass into the cell culture channels 104 in the direction of arrow 202 seen in Figure 2 of Wang, where the nutrients are limited by the size of the pores. It is seen in Figure 7 of Wang that the first layer can instead be first layer 701 that has a plurality of cell culture channels 704 that do not include designated cell culture chambers 122 such that cellular growth occurs within cell culture channels 704 (Wang; [0036]). It is understood that there would still be nests of pores 112 that are above the cell culture channels 704 along with a second layer 102 with microfluidic channels 108 above it.
It is seen in Figure 1 of Wang that there is a fluid inlet 114 that will be connected to a syringe pump for delivering fluids at a predetermined flow rate (Wang; [0027]). It is further described by [0041] of Wang that fluid inlets and outlets are exchangeable, which permits a number of drugs to be introduced. As example, there can be two inlets with eight outlets, or eight inlets with two outlets, where “The fluid inlets and fluid outlets are not necessarily at opposite ends of the cell array. Depending on the fluid pathway, the fluid inlet and/or fluid outlet may be positioned at another location.” (Wang; [0041]). It is specifically seen in Figure 4 of Wang where there are two inlets 414 that are understood to be holes in the surface of layer 402, which would be similar to how the outlets 118 in Figure 1 are shown.
It would have been obvious to one skilled in the art to modify the neurovascular unit-on-a-chip of Cha such that it includes the layer with the nest of pores and the corresponding layer with inlets that delivers fluid to the nest of pores as taught by Wang because Wang teaches that the pores provides a diffusion-controlled process, as nutrients in the fluid that pass into the cell culture channels are limited by the size of the pores (Wang; [0029]).
Layers 102 and 103 of Wang will now be placed on top of the substrate 10 of Cha, where each of the rows of pores will align with each of the channels 75. The underside of layer 103 of Wang is the upper interior surface, and the outer surface of layer 103 is the upper surface. Therefore, the nests of pores will extend through the body between the upper surface of the body and the upper interior surface of the body.
In the annotated Figure 1 supra, it has been indicated which channel 75 is being considered the passageway, along with a dashed box that encloses a channel 75 where a first row of nests of pores will be located and a second solid box that encloses a channel 75 that a second row of nests of pores will be located. From the annotated Figure 1 supra showing which channel 75 is being considered the passageway, the first group of nests of pores will be a first plurality of diffusion ports that extend between layer 103 of Wang at a location laterally spaced from the channel 75 (passageway as annotated above in Figure 1 showing the nest pores), where the first group of nests of pores will be axially spaced along a second axis that is laterally spaced from the first axis (axis along which channel 75 as annotated is located, a dashed line has been added that represents the first axis) extending through first and second sides of the chamber (please see the annotated Figure 1 above which indicates the sides and ends of the cell fixing well 20). The nests of pores of Wang will communicate with the ECM simulation material in the cell fixing well 20 (chamber) of Cha.
Further, there will be an inlet associated with a location of each of the channels 75 of Cha. As such, there will be an inlet port associated with the first group of nest pores (first loading port adjacent the first end of the chamber) and an inlet port associated with the second group of nest pores (second loading port adjacent the second end of the chamber). These inlets lay along a loading axis, which has been added to the annotated Figure 1 supra showing the nests of pores and passageway. Further, as seen in the annotated Figure 1 above that shows which shows which channel is being mapped to the passageway as well as the locations of the nest of pores, the ECM material (hydrogel) will be between the first and second inlet ports associated with the first and second group of nest pores and the annotated passageway such that the inlet ports and passageway are out of direct communication.
The nests of pores communicate with the inlet port described above, where the inlet port communicates with an environment external of the body.
As described by [0039] of Wang, the first, second, and third layers are made of a material such as PDMS. While Wang does not address gas permeability, it has been determined that where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In the current case, obviousness. Absent persuasive evidence that the PDMS materials are different, the prior art is considered to have the same properties with respect to gas permeability as that is claimed. MPEP § 2112.01 (I-IV).
Further, please see page 7 lines 10-12 and page 11 lines 27-28 of the instant specification which state that PDMS is a gas permeable material.
The limitation “the first plurality of diffusion ports are configured such that a first media deposited on the first plurality of diffusion ports diffuse into the hydrogel and forms a gradient of the first media in the hydrogel from the first end of the chamber to the second end of the chamber” is directed to the function of the apparatus and/or the manner of operating the apparatus, all the structural limitations of the claim has been disclosed by modified Cha and the apparatus of modified Cha is capable of depositing a first media on the first plurality of diffusion ports to form a gradient. As such, it is deemed that the claimed apparatus is not differentiated from the apparatus of modified Cha (see MPEP §2114).
Further, the first media is not positively recited in the claims, and is therefore not a part of the microfluidic device.
Regarding claim 30, modified Cha teaches the microfluidic device of claim 29. Modified Cha further teaches a second plurality of diffusion ports extending into the upper surface of the body and communicating with the chamber, the second plurality of diffusion ports axially spaced along an axis extending though the first and second sides of the chamber and parallel to the second axis along which the first plurality of diffusion ports is axially spaced.
Layers 102 and 103 of Wang are placed on top of substrate 10 of Cha such that each of the rows of nests of pores will align with each of the three channels 75, where each channel 75 will have its own group of nests of pores and where layer 103 of Wang will form the upper surface. From the annotated Figure 1 supra, it details which channel 75 is being considered the passageway where in the solid rectangle box encloses the location of the second group of nests of pores. This second group of nests of pores is a second plurality of diffusion ports that similarly extend into layer 103 (upper surface) and communicate with cell fixing well 20 (chamber), where the second group of nests of pores are axially spaced along an axis extending through first and second sides of cell fixing well 20 (chamber) and are parallel to the second axis along which the first group of nests of pores is.
Regarding claim 31, modified Cha teaches the microfluidic device of claim 29. Cha further teaches wherein the rod is movable between a first position wherein the rod is within the passageway in the hydrogel and a second position wherein the rod is removed from the hydrogel.
[0080] of Cha describes how channel 75 (see Figure 7) passing through ECM simulation material 70 is formed, where the ECM material includes “an extracellular matrix including at least one of collagen, fibronectin, fibrin, fibrinogen, elastin, hyaluronic acid, proteoglycan, laminin, heparin sulfate, chondroitin sulfate, keratin sulfate and Matrigel, hydrogel including at least one of alginate, polyethylene glycol, silicon hydrogel, polyacrylamide, polyethylene oxide, polypyrrolidone, glycosaminoglycan and polyhema, mixture of the extracellular matrix and hydrogel, chemical variant of the extracellular matrix, chemical variant of the hydrogel, or mixture of the chemical variant of the extracellular matrix and the chemical variant of the hydrogel.” [0084] of Cha describes where the forming of the channel 75 includes inserting micro-needle 60 into the first passage 35, cell fixing well 20, and the second passage 45, and then filling the cell fixing well 20 with an ECM simulation material in a sol state, where [0085] describes where the ECM simulation material in the sol state is formed along the micro-needle 60 in the cell fixing well 20 to cover and surround the micro-needle 60. [0087] of Cha then describes where the ECM simulation material 70 in the gel state may be formed by applying heat, where the micro-needle 60 then goes in a second direction D2 to be separated from the first passage 35 (see Figure 6 of Cha). Therefore, Figures 4 and 5 of Cha shows the micro-needle 60 (rod) in a first position where in Figure 5 of Cha it shows the micro-needle 60 (rod) in the ECM simulation material 70. Then in Figure 6 of Cha shows the micro-needle 60 (rod) being removed from the ECM simulation material 70. Figure 7 of Cha shows where the micro-needle 60 (rod) is fully removed, a second position.
Regarding claim 32, modified Cha teaches the microfluidic device of claim 29. Cha further teaches wherein the passageway is generally tubular.
It is seen in in Figure 4 of Cha that micro-needle 60 is inserted into the first passage 35 and second passage 45, where the micro-needles 60 are cylindrical, where Figure 2 of Cha shows a cross-sectional view of an extra-cellular matrix simulation material taken in region A (which is seen in Figure 1 of Cha). The cross section in Figure 2A is cylindrical. Therefore, it is the channel 75 will be generally tubular.
Regarding claim 33, modified Cha teaches the microfluidic device of claim 29. Cha further teaches wherein the passageway extends between the first and second sides of the chamber, the first axis of the passageway being closer to the first end of the chamber than the second end of the chamber.
The channel 75 that is being considered the passageway has been annotated in Figure 1 supra, where it is seen that the channel 75 (passageway) will extend along an axis (see annotated Figure 1 supra where the first axis has been added) between the first and second sides of the cell fixing well 20 (chamber) (see the annotated Figure 1 in relation to what is being considered sides versus ends), where this axis of the channel 75 (passageway) is closer to the first end of the cell fixing well 20 (chamber) than the second end of the cell fixing well 20 (chamber).
Claim(s) 8-9, 34-35 is/are rejected under 35 U.S.C. 103 as being unpatentable over Cha (US-2017/0211029-A1) and Wang (US-2019/0161715-A1), and in further view of Oviso (US-2009/0220948-A1).
Regarding claim 8, modified Cha teaches the microfluidic device of claim 1. Cha does not teach wherein the first end of the chamber is defined by a generally arcuate first end wall.
In the analogous art of microfluidic devices for transmitting, enclosing, and analyzing a fluid sample, Oviso teaches where a microfluidic device includes a reaction chamber (Oviso; [0001], [0050]).
Specifically, Oviso teaches where reaction chamber(s) 15 “may be of any shape… Examples of such shapes include, but are not limited to rectangle, square, ovoid, circular and bottle-like shapes. Optionally, a shape of the reaction chamber(s) may be selected that avoids or prevents the formation of air bubbles during the process of filling with fluid sample 31. Examples of means to avoid the formation of air bubbles include, but are not limited to, straight or convex walls or wall portions and rounded corners.” (Oviso; [0066]).
It would have been obvious to one skilled in the art to modify the shape of the cell fixing well of modified Cha such that it has rounded corners as taught by Oviso because Oviso teaches that rounded corners prevent the formation of air bubbles (Oviso; [0066]).
With rounded corners, the ends of the cell fixing well 20 (chamber) will be arcuate.
Regarding claim 9, modified Cha teaches the microfluidic device of claim 8. Oviso further teaches wherein the second end of the chamber is defined by a generally arcuate second end wall, see claim 8 supra.
Regarding claim 34, modified Cha teaches the microfluidic device of claim 29. Cha does not teach wherein the first end of the chamber is defined by a generally arcuate first end wall.
In the analogous art of microfluidic devices for transmitting, enclosing, and analyzing a fluid sample, Oviso teaches where a microfluidic device includes a reaction chamber (Oviso; [0001], [0050]).
Specifically, Oviso teaches where reaction chamber(s) 15 “may be of any shape… Examples of such shapes include, but are not limited to rectangle, square, ovoid, circular and bottle-like shapes. Optionally, a shape of the reaction chamber(s) may be selected that avoids or prevents the formation of air bubbles during the process of filling with fluid sample 31. Examples of means to avoid the formation of air bubbles include, but are not limited to, straight or convex walls or wall portions and rounded corners.” (Oviso; [0066]).
It would have been obvious to one skilled in the art to modify the shape of the cell fixing well of modified Cha such that it has rounded corners as taught by Oviso because Oviso teaches that rounded corners prevent the formation of air bubbles (Oviso; [0066]).
With rounded corners, the ends of the cell fixing well 20 (chamber) will be arcuate.
Regarding claim 35, modified Cha teaches the microfluidic device of claim 34. Oviso further teaches wherein the second end of the chamber is defined by a generally arcuate second end wall, see claim 34 supra.
Response to Arguments
Applicant arguments filed 12/03/2025 have been fully considered but are not persuasive.
Please note that due to amendments to the claims, the rejections in view of Cha and Wang have been modified to address these amendments.
Applicant argues on page 11 of 15 that claim 1 specifically requires the first plurality of diffusion ports to extend through the body between the upper surface of the body and the upper interior surface of the body, where none of the embodiments of Wang show or suggest this limitation and that the pores of Wang are provided in the third layers and disposed between the first and second layers.
Examiner respectfully disagrees. Currently, as the claim is written it only requires that the diffusion ports extend through the body between the upper surface of the body and the upper interior surface of the body, therefore so long as the pores extend between these two surfaces it will read on the claim. The claim does not require that the diffusion pores extend through the entirety of the upper surface and entirety of the upper interior surface.
Applicant further argues on page 12 of 15 that the examiner has provided no teaching or suggestion for the structure that the first plurality of diffusion ports communicate with the hydrogel in the chamber at a location laterally spaced from the passageway. Further that the examiner has provided no basis for repositioning the first plurality of diffusion ports to communicate with the material defining the passageway through the microfluidic array, not the passageway itself.
Firstly, it is noted that while some repositioning will be required, each of the three passageways of Cha will be associated with its own group of nests of pores. Secondly, there is nothing in the claim that limits there being additional passageways from being present, where therefore as there are multiple passageways and multiple groups of nests of pores associated with each passageway, mapping can be done to each component as it is again emphasized that there is no limitation on how many passageways or diffusion ports that may be present. Finally, please see page 9 of this Office Action which provides reasoning for incorporating the teachings of Wang, the same as the reasoning provided in the previous Office Action. The reasoning is not a mere conclusory statement.
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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/S.Y.L./Examiner, Art Unit 1796
/ELIZABETH A ROBINSON/Supervisory Patent Examiner, Art Unit 1796