DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Claims
Claims 1-15 and 17-21 remain pending in the application.
Claim Objections
Claims 3, 5, 13, 17 are objected to because of the following informalities:
Claim 3 currently has the abbreviation “CSF” fluid, where this abbreviation should be written out before using the abbreviated term. Additionally, “CSF” is understood to be the abbreviation for cerebrospinal fluid, and therefore “CSF fluid” appears to be redundant.
Therefore claim 3 should be amended to recite “cerebrospinal fluid (CSF), or a combination”
Claim 5 currently recites “wherein said compressible substrate comprises an adhesive membrane positioned between a channel plate positioned adjacent and a base plate.” where the phrasing makes it difficult to understand what the claim is describing. It sounds as though the compressible substrate comprises an adhesive membrane, and this membrane is positioned between a channel plate, where the channel plate is adjacent to the membrane, and there is a base plate. It almost sounds like something needs to come after “between a channel plate positioned adjacent” before concluding with “and a base plate”.
On page 15 starting on line 9 of the instant specification, it describes Figure 22 where the microfluidic device 300 housing secures a compressible substrate (314) having an adhesive membrane (308) positioned between a channel plate (307) and base plate (309).
Therefore, it is believed that it would be more clear for claim 5 to recite “wherein said compressible substrate comprises an adhesive membrane positioned between a channel plate
Claim 13 is currently missing a period at the end of the claim. Please see MPEP 608.01(m) which states that claims must end with a period.
Further, the phrasing of claim 13 reads awkwardly and it is suggested to amend line 2 to recite “through said one or more calibrated springs.” where it is now “springs” because as described in claim 12 there are one or more calibrated springs.
Claim 17 recites “along light pathway.” on line 2 where it is suggested to amend line 2 to recite “along a light pathway.” as this would make the claim read more smoothly.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-15, 17-21 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites “a microfluidic device adapted to hold a biological sample within an active area of a compressible substrate;” on lines 2-3, where it is unclear if the compressible substrate is a required part of the cell imaging system or not.
Currently, the compressible substrate is not positively recited in the claim, and is therefore not a part of the cell imaging system. However, later dependent claims such as 5-6, and 9 further limit the compressible substrate.
Therefore, for examination there will be a rejection set forth for when the compressible substrate is not required and a rejection set forth for when the compressible substrate is required.
It is suggested that if the compressible substrate is a required part of the system, to amend claim 1 to recite:
A cell imaging system comprising:
- a compressible substrate with an active area;
- a microfluidic device adapted to hold a biological sample within [[an]] the active area of [[a]] the compressible substrate;
Or similar that will make it clear that the compressible substrate is a part of the claimed cell imaging system.
Claims 2-15, 17-21 are rejected by virtue of being dependent on a rejected claim.
Claim 6 recites “an active area.” on lines 2-3, where it is unclear if this active area is the same or different from the active area described on line 2 of claim 1.
For examination, it will be interpreted that they are the same active area.
Claim 7 is rejected by virtue of being dependent on a rejected claim.
Claim 8 recites “said microfluidic channels” on line 1 where there is insufficient antecedent basis for this limitation, as no microfluidic channels have been recited prior.
While claim 6 does describe the channel plate comprising a first microfluidic channel and a second microfluidic channel on the adhesive membrane, it is unclear if both the channels of the channel plate and adhesive membrane are hydrophilic.
Page 8 lines 12-16 do describe the microfluidic channel 13 of the housing 4 may include a hydrophilic inner surface, page 11 lines 15-17 describe Figure 9 and that microfluidic channel 113 may include a hydrophilic inner surface, and page 13 lines 21-23 describing Figure 14 that microfluidic channel 226 may have a hydrophilic inner surface. However, it is not seen in the instant specification where it is described that the microfluidic channel on the adhesive membrane is hydrophilic.
Therefore, for examination it will be interpreted that claim 8 is dependent on claim 6, and that the microfluidic channel being referenced is the microfluidic channel of the channel plate.
Claim 14 recites “wherein each cylinder is responsive to a calibrated spring” on line 2 where it is unclear if this calibrated spring is the same or different from the one or more calibrated spring described in claim 13.
For examination, it will be interpreted that they are the same calibrated spring.
Claim 17 recites “wherein said light source is responsive to said compression assembly” on lines 1-2, where it is unclear what it means for the light source to be “responsive” to the compression assembly. Does this mean that the light source turns on due to the compression assembly? Or does it mean it moves with the compression assembly?
For examination, it will be interpreted that the light source reacting to the compression assembly will read on it being “responsive”.
Claims 18-19 are rejected by virtue of being dependent on a rejected claim.
Claim 18 recites “a compression cell that is responsive to said compression assembly” where it is unclear what it means for the compression cell to be “responsive” to the compression assembly.
Similar to above, claim 18 will be interpreted that the compression cell needs to react to the compression assembly in some way for it to be “responsive”.
Lines 2-3 recites “a compression force”, where it is unclear if this compression force is the same or different from the one described on line 4 of claim 1.
For examination it will be interpreted that they are the same.
Claim 21 recites “said compression cell” on line 1, where there is insufficient antecedent basis for this limitation, as no compression cell has been recited prior.
Additionally, line 2 recites “the housing” where there is insufficient antecedent basis for this limitation, as no housing has been recited prior.
It is noted that claim 18 describes a compression cell, however does not describe a housing.
Claim 4 describes a housing, but does not describe a compression cell.
For examination, it will be interpreted that claim 21 is dependent on claim 18, where the housing will be interpreted to be a structure of the microfluidic device.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1-15, 17-19, 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hajipouran Benam (US-2020/0055054-A1) herein Hajipouran, in view of West (US-2006/063160-A1).
Please note the rejection set forth below is for when the compressible substrate is not a required component of the cell imaging system.
Regarding claim 1, Hajipouran teaches a cell imaging system comprising:
- a microfluidic device (organ-on-a-chip (OOC) device 10) ([0034], Figures 1-2);
- a compression assembly (clamping system 300) configured to apply a compression force ([0067], Figures 3A-C);
- wherein said device (10) is configured to allow an imaging device to image or observe while said compression force is applied to said compressible substrate ([0037] see OOC 10 has an optical window that permits viewing of the fluids, media, particulates, etc., [0064] see a glass slide or other transparent window can be integrated into the clamp device to provide a rigid support for the microfluidic device which improves pressure distribution for flexible devices while enabling good optical access for macroscopic, visual, or microscopic imaging that may be desirable through viewing portions of the clamp system).
Please note that the limitations “a microfluidic device adapted to hold a biological sample within an active area of a compressible substrate”, “a compression assembly configured to apply a compression force to said compressible substrate forming a cell monolayer within said active area”, “said device is configured to allow an imaging device to image or observe the cell monolayer within the active area while said compression force is applied to said compressible substrate.” are 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 Hajipouran and the apparatus of Hajipouran is capable of the OOC device holding a biological sample within an active area of a compressible substrate, the clamping system is capable of applying a compression force to form a cell monolayer within the active area, and the OOC device is capable of allowing an imaging device to image or observe the cell monolayer while compression force is applied. As such, it is deemed that the claimed apparatus is not differentiated from the apparatus of Hajipouran (see MPEP §2114).
Please note that the biological sample (and thus cell monolayer), compressible substrate, and imaging device have not been positively recited and are therefore not a part of the claimed system.
[0069] describes where base 370 of the clamping system includes an aperture 355 extending therethrough, where the aperture allows for placement of a glass slide into the base 370 and is positioned to support the microfluidic device between the glass slide and compression plate 314. While [0037] describes image-gathering techniques such as spectroscopy and microscopy, Hajipouran does not teach:
- a light source directed to said active area; and
In the analogous art of illuminating a microfluidic chip, West teaches an illuminator (West; [0005]).
Specifically, West describes where a system includes a microfluidic chip, an illuminator, and a detector (West; [0005]). [0026] of West describes that suitable detectors typically include a microscope scanner, where [0032] describes suitable illuminators to be light emitting diodes. As seen in Figure 3, a compression backing plate 40 will support microfluidic chip 30, where the compression backing plate 40 includes illuminator notches 54 for positioning a suitable illuminator (West; [0040]).
It would have been obvious to one skilled in the art to modify the base of Hajipouran, which supports the microfluidic device, such that it includes illuminator notches and the illuminator as taught by West because West teaches that it is desirable to include an illumination source for microscope scanners (West; [0022], [0026]).
Regarding claim 2, modified Hajipouran teaches the system of claim 1.
The limitations of claim 2 are directed to the material worked upon by the apparatus, all the structural limitations of the claim have been disclosed by modified Hajipouran and the apparatus of modified Hajipouran is capable of working on live cells. As such, it is deemed that the claimed apparatus is not differentiated from the apparatus of modified Hajipouran (see MPEP §2115).
Further, the biological sample has not been positively recited in the claim, and is therefore not a part of the claimed system.
Please note that [0035] of Hajipouran describes a bilayer of cells that are within the OOC device 10.
Regarding claim 3, modified Hajipouran teaches the system of claim 1.
The limitations of claim 3 are directed to the material worked upon by the apparatus, all the structural limitations of the claim has been disclosed by modified Hajipouran and the apparatus of modified Hajipouran is capable of working on blood, serum, urine, saliva, CSF fluid, peritoneal fluid, or a combination of the same, all of the foregoing optionally containing one or more live cells. As such, it is deemed that the claimed apparatus is not differentiated from the apparatus of modified Hajipouran (see MPEP §2115).
Further, the biological sample has not been positively recited in the claim, and is therefore not a part of the claimed system.
Regarding claim 4, modified Hajipouran teaches the system of claim 1. Hajipouran further teaches wherein said microfluidic device (10) comprises a housing (upper body segment 12a and lower body segment 12b) (Hajipouran; [0034], Figures 1-2).
Please note that the compressible substrate is currently not positively recited in the claim, and is therefore not a part of the claimed system.
As seen in Figure 2 of Hajipouran there is a membrane 40 that is positioned between the upper body segment 12a and lower body segment 12b that is being considered the compressible substrate. Therefore, upper and lower body segments 12a and 12b are capable of securing membrane 40.
Regarding claim 5, modified Hajipouran teaches the system of claim 4. The limitations of claim 5 are directed to the compressible substrate, which is currently not positively recited and is therefore not a part of the claimed system. Because the limitations of claim 5 are directed to a component that is not required, the limitations of claim 5 are considered to be met.
Regarding claim 6, modified Hajipouran teaches the system of claim 5. The limitations of claim 6 are directed to the compressible substrate, which is currently not positively recited and is therefore not a part of the claimed system. Because the limitations of claim 6 are directed to a component that is not required, the limitations of claim 6 are considered to be met.
Regarding claim 7, modified Hajipouran teaches the system of claim 6. Hajipouran further teaches wherein said housing (12a and 12b) comprises an input position (see ports for first fluid inlet 14 and second fluid inlet 24) and an output position (see ports for exit channel 31 and outlet channel 33) (Hajipouran; [0034], Figure 1).
Please note that the limitation “in fluid communication with the first and second microfluidic channels.” is directed to the compressible substrate, as the compressible substrate has the channel plate that has a first microfluidic channel and a second microfluidic channel on the adhesive membrane. Because the compressible substrate has not been positively recited and is therefore not a part of the claimed system, the limitation regarding the microfluidic channels are considered to be met.
However, please see Figure 1 of Hajipouran, the ports for the fluid inlet 14, second fluid inlet 24, exit channel 31 and outlet channel 33 are connected to either upper or lower microchannel 34 or 36.
Regarding claim 8, modified Hajipouran teaches the system of claim 5. The limitation of claim 8 is directed to the compressible substrate, which is currently not positively recited and is therefore not a part of the claimed system. Because the limitations of claim 8 are directed to a component that is not required, the limitations of claim 8 are considered to be met.
Regarding claim 9, modified Hajipouran teaches the system of claim 5. The limitations of claim 9 are directed to the compressible substrate, which is currently not positively recited and is therefore not a part of the claimed system. Because the limitations of claim 9 are directed to a component that is not required, the limitations of claim 9 are considered to be met.
Regarding claim 10, modified Hajipouran teaches the system of claim 4. Hajipouran further teaches wherein said housing (10) is constructed substantially of a non-compressible material (Hajipouran; [0034] see the upper and lower body segments 12a and 12b of OOC device 10 are made of PDMS or polycarbonate).
Regarding claim 11, modified Hajipouran teaches the system of claim 1. Hajipouran further teaches wherein said compression assembly (300) comprises a spring-actuated compression assembly (Hajipouran; Figures 3A-C which shows the clamping system 300, [0068] describes there being springs 317 and 318. Therefore, the clamping system 300 seen in Figures 3A-C comprises a spring-actuated compression assembly).
Regarding claim 12, modified Hajipouran teaches the system of claim 11. Hajipouran further teaches wherein said spring-actuated compression assembly comprises a bottom compression panel (compression plate 314) coupled with a top compression panel (top cover 360) by one or more calibrated springs (springs 317, 318) (Hajipouran; [0068], Figures 3A-C).
Regarding claim 13, modified Hajipouran teaches the system of claim 12. Hajipouran further teaches wherein a force applied to said top compression panel (360) is transmitted to said bottom compression panel (340) through said one or more calibrated spring (317 and 318) (Hajipouran; [0068] see Figures 3A-C, [0090] describing where the compression plate is urged upward as seen in Figure 7B. One skilled in the art would understand that an upward force is applied to the cover that is then transferred through the springs into a downward force on the compression plate).
Regarding claim 14, modified Hajipouran teaches the system of claim 13. Hajipouran further teaches wherein said spring-actuated compression assembly comprises one or more cylinders (posts 330 and 340), wherein each cylinder (330, 340) is responsive to a calibrated spring (317, 318) and secured by a lower and upper support post (Hajipouran; [0071] see springs 317 and 318 can extend around an outer boundary of their respective vertical posts 330, 340, Figure 3A).
[0053] of Hajipouran describes that the design of the posts illustrated are illustrated with a square or rectangular cross-section, the shape of the post itself can be that of any geometric entity that allows a compression device, such as a spring, to apply the needed force to the compression plate. Therefore, one skilled in the art would find it obvious that the posts 330 and 340 may be cylindrical in shape.
Additionally it has been held that changing the shape of a component is a matter of choice which a person of ordinary skill in the art would have found obvious absent persuasive evidence that the particular shape of the claimed component was significant, please see MPEP 2144.04 IV. B.
The posts 330 and 340 seen in Figure 3A are seen to connect to support structures 332 and 342, where support structure 332 is a lower support post and 342 is an upper support post.
Regarding claim 15, modified Hajipouran teaches the system of claim 13.
The limitation “wherein said spring-actuated compression assembly can be calibrated to adjust the orientation or morphology of the cells in the monolayer.” 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 Hajipouran and the apparatus of modified Hajipouran is capable of being calibrated to adjust the orientation or morphology of the cells in the monolayer. As such, it is deemed that the claimed apparatus is not differentiated from the apparatus of modified Hajipouran (see MPEP §2114).
Further, the sample, and thus the cells and monolayer, have not been positively recited in the claim, and are therefore not a part of the claimed system.
Regarding claim 17, modified Hajipouran teaches the system of claim 1. Hajipouran has been modified such that the base 370 will include illuminator notches and the illuminator as taught by West. As the illuminator is now a part of the clamping system, one skilled in the art would find it obvious that when the clamping system is moved, the illuminator will move with the clamping system and thus be responsive to the clamping system.
Further, the path of the illuminator will define a light pathway.
Regarding claim 18, modified Hajipouran teaches the system of claim 17. Hajipouran has been modified such that the base 370 will include the illuminator notches and the illuminator as taught by West.
The base 370 of Hajipouran is a compression cell, where based on [0069] of Hajipouran the compression plate 314 will compress the microfluidic device against the glass slide held by the base 370. Therefore, the base 370 is responsive to the clamping system and is adapted to transmit the compression force to the OOC device 10.
Regarding claim 19, modified Hajipouran teaches the system of claim 17. Hajipouran has been modified such that the base will now include the illuminator notches and illuminator as taught by West.
[0079] of Hajipouran describes in reference to Figure 4A showing clamping system 400 that the base 470a has a glass slide 416a positioned in the center of the base 470a above an aperture that defines a viewing window through the base 470a, where a microfluidic device is then placed on the glass slide 416a. One skilled in the art would find it obvious that the base 370 see in Figure 3 of Hajipouran will similarly act as a window.
Hajipouran does not teach that the base comprises a guide adaptor positioned along the light pathway within a compression slot having a viewing surface adjacent to said active area on said microfluidic device.
West further teaches where compression backing 40 includes a beveled channel 72 that provides a viewing port 74 for viewing the microfluidic chip, where the beveled channel 72 can hold an optical fiber bundle or other waveguide for transmitting light from the microarray through the transparent backing plate 70 to a suitable detector.
It would have been obvious to one skilled in the art to modify the base of Hajipouran such that it includes a viewing port that aligns with the microfluidic device in the area desired to be imaged, where the viewing port is connected with an optical fiber bundle as taught by West because West teaches that the fiber optic bundles are effective for transmitting light from a microfluidic chip to a detector (West; [0046]).
Regarding claim 21, modified Hajipouran teaches the system of claim 18, please see 112b section supra regarding claim 21’s dependency.
Figure 6 of Hajipouran shows an example of microfluidic system 600 that has a microfluidic device 612 that has been placed in a clamping device, where the base 670 is seen to have an overhanging surface in comparison to the microfluidic chip 612 (Hajipouran; [0085], [0086]). One skilled in the art would find it obvious that the microfluidic device placed in the clamping system 300 seen in Figure 3A will be the same as that seen in Figure 6.
The limitation “to prevent extended transit of the compression cell.” 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 Hajipouran and the overhang of base 370 of Hajipouran is capable of preventing extended transit of the base. As such, it is deemed that the claimed apparatus is not differentiated from the apparatus of modified McNeely (see MPEP §2114).
Claim(s) 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hajipouran Benam (US-2020/0055054-A1) herein Hajipouran, and West (US-2006/063160-A1), and in further view of Yoder (US-2006/0094108-A1).
Regarding claim 20, modified Hajipouran teaches the system of claim 1. Hajipouran has been modified with West such that the base includes illuminator notches and the illuminator of West, where [0032] of West describes that the illuminators typically include light emitting diodes. However, Hajipouran nor West describe an optical diffuser positioned between said light source and a viewing surface.
In the same problem solving area of illuminating a target area through the use of one or more light emitting diodes, Yoder teaches that a light shaping diffuser may be placed on the output end of a light emitting diode to shape the light and provide better illumination uniformity (Yoder; [0139], [0140]).
It would have been obvious to one skilled in the art to modify the illuminator of modified McNeely such that it further includes a light shaping diffuser on its output end as taught by Yoder because Yoder teaches that the diffuser allows for better illumination uniformity (Yoder; [0140]).
Claim(s) 1-8, 10, 17-19, 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over McNeely (US-2004/0037739-A1) in view of West (US-2006/0063160-A1).
Please note that the following rejection set forth is if the compressible substrate is a required component of the cell imaging system.
Regarding claim 1, McNeely teaches a cell imaging system comprising:
- a microfluidic device (main interface layer 617 and base 402 ([0083] cites as base “102”, however this is understood to be a typo as later the base is reference number 402. Herein the base will be 402)) adapted to hold a biological sample within an active area (microarray 154) of a compressible substrate (microarray slide 150 and gasket 404) ([0083], Figure 2);
- a compression assembly (clamp mechanism 418 and 420) configured to apply a compression force to said compressible substrate (150 and 404) ([0083], Figure 2);
- wherein said device (617, 402) is configured to allow an imaging device to image or observe within the active area (154) while said compression force is applied to said compressible substrate (150 and 404) ([0155] see detection may be performed while the interface device is attached to the slide, proving the interface device includes a viewing window to permit visual access to the slide).
The limitations “a microfluidic device adapted to hold a biological sample within an active area of a compressible substrate”, “a compression assembly configured to apply a compression force to said compressible substrate forming a cell monolayer within said active area”, and “wherein said device is configured to allow an imaging device to image or observe the cell monolayer within the active area while said compression force is applied to said compressible substrate.” are 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 McNeely and the apparatus of McNeely is capable of the microfluidic device holding a biological sample within an active area of a compressible substrate, the clamp mechanism is capable of applying a compression force to form a cell monolayer within the active area, and the microfluidic device is capable of allowing an imaging device to image or observe the cell monolayer while compression force is applied. As such, it is deemed that the claimed apparatus is not differentiated from the apparatus of McNeely (see MPEP §2114).
Further, please note that the biological sample (and thus cell monolayer) and imaging device have not been positively recited and are therefore not a part of the claimed system.
[0138] of McNeely describes that the interface device may include various types of sensors that include optical sensors for real-time detection of reactions occurring in the interface device, and [0155] describes that detection-binding molecules from the binding solution to molecules on the microarray slide is typically determined by detecting fluorescence, radioactivity, color change, and so forth occurring at sites where binding occurred where a specific example for the binding molecule in the binding solution is labeled with a fluorescent dye, the sites where binding has occurred fluoresce. However, McNeely does not provide specifics on the optical sensors and therefore does not teach a light source directed to said active are.
In the analogous art of microarray analysis, West teaches a system that includes a manifold, a microfluidic chip comprising a microarray, an illuminator for proving light, and a detector in optical communication with the microarray (West; [0005]).
Specifically, West teaches where suitable signals of the microarray include fluorescence (West; [0022]). [0032] of West describes that illuminators are typically adjacently secured to the microfluidic chip to provide a source of excitation illumination to the analyte molecules situated on the microarray. [0032] further describes that the illuminator is not necessarily fixed to the microfluidic chip and that in preferred embodiments the illuminator is secured to the edge of the microfluidic chip using a suitable holder such as a compression fitting, holding bar, or screw.
It would have been obvious to one skilled in the art to modify the interface device of McNeely such that it includes a holder and an illuminator as taught by West because West teaches that it is desirable for fluorescent microarrays to include an illuminator that excites the fluorescent probes that are attached to the microarray which is then detected by a detector (West; [0022], [0034]).
Additionally, McNeely is silent with regards to specific optical sensors, therefore, it would have been necessary and thus obvious to look to the prior art for conventional optical sensors. West provides this conventional teaching showing that it is known in the art to use both a detector and an illuminator for microarrays. Therefore, it would have been obvious to one having ordinary skill in the art to include an illuminator as a part of the optical sensor because it is taught by West that illuminators are effective for detection in microarrays.
Regarding claim 2, modified McNeely teaches the system of claim 1.
The limitations of claim 2 are directed to the material worked upon by the apparatus, all the structural limitations of the claim have been disclosed by modified McNeely and the apparatus of modified McNeely is capable of working on live cells. As such, it is deemed that the claimed apparatus is not differentiated from the apparatus of modified McNeely (see MPEP §2115).
Further, the biological sample has not been positively recited in the claim, and is therefore not a part of the claimed system.
Please see [0007] of McNeely which describes the microarrays used in the invention, where it states that cultured cells may also be grown onto microarrays.
Regarding claim 3, modified McNeely teaches the system of claim 1.
The limitations of claim 3 are directed to the material worked upon by the apparatus, all the structural limitations of the claim have been disclosed by modified McNeely and the apparatus of modified McNeely is capable of working on blood, serum, urine, saliva, CSF fluid, peritoneal fluid, or a combination of the same, all of the foregoing optionally containing one or more live cells. As such, it is deemed that the claimed apparatus is not differentiated from the apparatus of modified McNeely (see MPEP §2115).
Further, the biological sample has not been positively recited in the claim, and is therefore not a part of the claimed system.
Regarding claim 4, modified McNeely teaches the system of claim 1. McNeely further teaches wherein said microfluidic device (617 and 402) comprises a housing securing the compressible substrate (150 and 404) (McNeely; see Figure 2 where the main interface layer 617 and base 402 are a housing, and Figure 3 which shows the assembled device where the main interface layer 617 and base 402 will secure the microarray slide 150 and gasket 404).
Regarding claim 5, modified McNeely teaches the system of claim 4. McNeely further teaches wherein said compressible substrate (150 and 404) comprises an adhesive membrane positioned between a channel plate (404) positioned adjacent and a base plate (150) (McNeely; [0110] describes the gaskets used, where it is effective to provide both clamping and an adhesive layer where the clamping functions to increase the strength of the bond provided by the adhesive, [0123] describes where a gasket may be provided with a sticky or tacky material or adhesive on some or all of its lower surface such that it may be moved for positioning with respect to microarray slide 150 but once in a suitable position it can be secured to the microarray slide 150 by applying pressure).
Regarding claim 6, modified McNeely teaches the system of claim 5. McNeely further teaches said channel plate (404) comprises a first microfluidic channel in fluid communication with a second microfluidic channel on the adhesive membrane forming an active area (154) (McNeely; [0083] describes that the boundaries of a reaction chamber is defined by opening 406 in gasket 404, where this reaction chamber is a channel. Further, as described in [0110] and [0123] that an adhesive may be placed on the underside of the gasket and therefore the adhesive will be in the same shape as the gasket to define a second channel, where both of these channels are in fluid communication with one another).
Regarding claim 7, modified McNeely teaches the system of claim 6. McNeely further teaches wherein said housing (617, 402) comprises an input position (inlet 612) and an output position (outlet 614) in fluid communication with the first and second microfluidic channels (McNeely; [0083], Figure 2).
Regarding claim 8, modified McNeely teaches the system of claim 5. McNeely further teaches wherein said microfluidic channels comprises hydrophilic inner surfaces (McNeely; [0109] describes that the interface device, which includes both the main interface layer 617 and the gasket 404 described in [0083], may be formed of hydrophilic materials. Therefore, when the interface layer 617 is made of a hydrophilic material then the reaction chamber (reaction chamber being the channel as described in claim 6 supra) will have inner surfaces that are hydrophilic).
Regarding claim 10, modified McNeely teaches the system of claim 4. McNeely further teaches wherein said housing (617 and 402) is constructed substantially of a non-compressible material (McNeely; [0083] see lower surface of main interface layer 617 can be formed of a membrane of a thin flexible membrane attached to a more rigid material which forms the bulk of main interface layer 617 or the lower surface may be formed of the same material as the remainder of main interface layer 617).
Additionally, one skilled in the art would find it obvious that since the base 402 and interface layer 617 are clamped via C-channel clamps, the material of the interface layer 617 and base 602 being on the outermost sides would need to be made of a material that is substantially non-compressible.
Regarding claim 17, modified McNeely teaches the system of claim 1. McNeely has been modified with West such that the interface device includes an illuminator. As described by [0050] of West that discusses microarray preparation and detection, a typical microarray is performed after the microarray is spotted and has been hybridized for approximately 12 hours, and after the incubation the microarray is washed and the probes or spots are illuminated with the illuminator and the emission is detected using a CCD detector.
Therefore, one skilled in the art would recognize that the illuminator of West will be responsive to the clamp mechanism (compression assembly) of McNeely because the device of McNeely would need to be fully assembled before the microarray is analyzed and subsequently illuminated by the illuminator. Further, the path that the illuminator lights is a light pathway.
Regarding claim 18, modified McNeely teaches the system of claim 17. McNeely has been modified by West such that it includes a holder and illuminator as taught by West.
[0040] of West describes Figure 3 showing a compression backing plate 40 that includes two illuminator notches 54 for positioning a suitable illuminator, the compression backing plate 40 understood to be the holder described in [0032].
Therefore, West teaches where the illuminator (light source) is positioned within a compression backing plate (compression cell), and the interface device along with the base and microarray slide of McNeely will be held by the compression backing plate.
Because the interface device and microarray slide of McNeely, which includes the clamp mechanism, will be placed in the compression backing plate of West, the compression backing plate is therefore responsive to the clamp mechanism (compression assembly).
Additionally, because the compression backing plate of West supports the device of McNeely, the compression backing plate will indirectly transmit the compression force to the device of McNeely.
Regarding claim 19, modified McNeely teaches the system of claim 17. McNeely has been modified with West to include the holder (later described to be a compression backing) and illuminator.
[0044] of West describes that the compression backing 40 includes a beveled channel 72 that provides a viewing port 74 for viewing the microfluidic chip, where the beveled channel 72 can hold an optical fiber bundle or other waveguide for transmitting light from the microarray through the transparent backing plate 70 to a suitable detector.
It would have been obvious to one skilled in the art to modify McNeely such that it further includes the optical fiber bundle as taught by West because West teaches that the fiber optic bundles are effective for transmitting light from a microfluidic chip to a detector (West; [0046]).
The compression backing 40 (compression cell) will comprise an optical fiber bundle (guide adaptor) that is positioned along the pathway of light from the illuminator within the viewing port (compression slot) of the compression backing, where the viewing port of the compression backing will be adjacent to the microarray of McNeely.
Regarding claim 21, modified McNeely teaches the system of claim 18, please see 112(b) section supra regarding claim 21’s dependency.
McNeely has been modified with West such that there is now the compression backing plate with illuminator that supports the device of McNeely, where as seen in Figure 6 that the compression backing plate 40 has parts that overhang the microfluidic chip 30.
The limitation “to prevent extended transit of the compression cell.” 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 McNeely and the overhang of compression backing plate of West is capable of preventing extended transit of the compression backing. As such, it is deemed that the claimed apparatus is not differentiated from the apparatus of modified McNeely (see MPEP §2114).
Claim(s) 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over McNeely (US-2004/0037739-A1), and West (US-206/0063160-A1) and in further view of Kurabayashi (US-2022/0387995-A1).
Regarding claim 9, modified McNeely teaches the system of claim 5. McNeely further teaches wherein said channel plate (404) comprises a silicone channel plate (McNeely; [0110] see gasket may be formed of silicone, Figure 2), said adhesive membrane comprises a pressure sensitive adhesive (McNeely; [0123] see pressure sensitive adhesive).
McNeely describes in [0006] that the microarray is normally formed on a planar substrate such as a glass microscope slide, therefore McNeely does not teach that the microarray slide 150 (base plate) comprises a cyclic block copolymer (CBC).
In the analogous art of biomarker detectors, Kurabayashi teaches a microfluidic chip that comprises a plurality of barcode channels (Kurabayashi; [0015]).
Specifically, Kurabayashi teaches where a sensor 200 includes a microfluidic chip 202 disposed between an illumination source 204 and a photodetector array 206 (Kurabayashi; [0055], Figure 3). As further described in [0056], the microfluidic chip has a plurality of nanoplasmonic barcode detectors that are each configured through antibody conjugation to capture a different biomarker. [0057] describes that the microfluidic chip may be formed of a substrate made of polymethyl methacrylate, polycarbonate, polystyrene, polyvinyl chloride, polyimide, and the family of cyclic olefin polymers including cyclic block copolymer, and glass.
Examiner further finds that the prior art contained a device/method/product (i.e., reaction device including a microarray slide) which differed from the claimed device by the substitution of component(s) (i.e., microarray slide being a glass microscope slide) with other component(s) (i.e., microarray slide comprising a cyclic block copolymer), and the substituted components and their functions were known in the art as above set forth. An ordinarily skilled artisan could have substituted one known element with another (i.e., the glass for cyclic block copolymer), and the results of the substitution (i.e., creation of a microarray on the surface and subsequent detection) would have been predictable.
Therefore, pursuant to MPEP §2143 (I), Examiner concludes that it would have been obvious to an ordinarily skilled artisan to substitute the glass material for the microarray slide of reference McNeely with a cyclic block copolymer of reference Kurabayashi, since the result would have been predictable.
Claim(s) 11-15 is/are rejected under 35 U.S.C. 103 as being unpatentable over McNeely (US-2004/0037739-A1) and West (US-2006/0063160-A1), and in further view of Hajipouran (US-2020/0055054-A1).
Regarding claim 11, modified McNeely teaches the system of claim 1. While McNeely teaches that the interface device and slide 150 are clamped together with a clamp mechanism such as C-channel clamps 418 and 420 (McNeely; [0083]), McNeely does not teach wherein said compression assembly comprises a spring-actuated compression assembly.
In the same problem solving area of clamping systems for microfluidic devices, Hajipouran teaches where the clamping system includes a base 370, vertical posts 330 and 340, a top cover 360, compression plate 314, and springs 317 and 318 (Hajipouran; [0009], [0068]).
Specifically, Hajipouran describes where the compression plate 314 under the action of the springs 317 and 318 applies a substantially uniform pressure to a top surface of a microfluidic device that is placed between the compression plate 317 and base 370 (Hajipouran; [0068]). [0064] of Hajipouran further describes that a transparent window can be integrated into the clamp device that enables good optical access for macroscopic, visual, or microscopic imaging that may be desirable through viewing portions of the clamp system.
Examiner further finds that the prior art contained a device/method/product (i.e., reaction device) which differed from the claimed device by the substitution of component(s) (i.e., clamping mechanism such as C-channel clamps) with other component(s) (i.e., a spring-actuated compression assembly), and the substituted components and their functions were known in the art as above set forth. An ordinarily skilled artisan could have substituted one known element with another (i.e., the C-channel clamps for the clamping system with compression plate, base, vertical posts, top cover, and springs), and the results of the substitution (i.e., compression of the interface device and the slide) would have been predictable.
Therefore, pursuant to MPEP §2143 (I), Examiner concludes that it would have been obvious to an ordinarily skilled artisan to substitute the C-channel clamps of reference McNeely with the clamping system seen in Figure 3A of reference Hajipouran, since the result would have been predictable.
Regarding claim 12, modified McNeely teaches the system of claim 11. Hajipouran further teaches wherein said spring-actuated compression assembly comprises a bottom compression panel (compression plate 314) coupled with a top compression panel (top cover 360) by one or more calibrated springs (springs 317, 318) (Hajipouran; [0068], Figure 3A).
Regarding claim 13, modified McNeely teaches the system of claim 12. Hajipouran further teaches wherein a force applied to said top compression panel (360) is transmitted to said bottom compression panel (314) through said one or more calibrated spring (317, 318) (Hajipouran; [0068] see Figures 3A-C, [0090] describing where the compression plate is urged upward as seen in Figure 7B. One skilled in the art would understand that an upward force is applied to the cover that is then transferred through the springs into a downward force on the compression plate).
Regarding claim 14, modified McNeely teaches the system of claim 13. Hajipouran further teaches wherein said spring-actuated compression assembly comprises one or more cylinders (posts 330 and 340), wherein each cylinder (330, 340) is responsive to a calibrated spring (317, 318) and secured by a lower and upper support post (Hajipouran; [0071] see springs 317 and 318 can extend around an outer boundary of their respective vertical posts 330, 340, Figure 3A).
Further, [0053] of Hajipouran describes that the design of the posts illustrated are illustrated with a square or rectangular cross-section, the shape of the post itself can be that of any geometric entity that allows a compression device, such as a spring, to apply the needed force to the compression plate. Therefore, one skilled in the art would find it obvious that the posts 330 and 340 may be cylindrical in shape.
Additionally it has been held that changing the shape of a component is a matter of choice which a person of ordinary skill in the art would have found obvious absent persuasive evidence that the particular shape of the claimed component was significant, please see MPEP 2144.04 IV. B.
The posts 330 and 340 seen in Figure 3A are seen to connect to support structures 332 and 342, where support structure 332 is a lower support post and 342 is an upper support post.
Regarding claim 15, modified McNeely teaches the system of claim 13.
The limitation “wherein said spring-actuated compression assembly can be calibrated to adjust the orientation or morphology of the cells in the monolayer.” 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 McNeely and the clamping system of Hajipouran is capable of being calibrated to adjust the orientation or morphology of the cells in the monolayer. As such, it is deemed that the claimed apparatus is not differentiated from the apparatus of modified McNeely (see MPEP §2114).
Further, the sample, and thus the cells and monolayer, have not been positively recited in the claim, and are therefore not a part of the claimed system.
Claim(s) 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over McNeely (US-2004/0037739-A1) and West (US-2006/0063160-A1), and in further view of Yoder (US-2006/0074108-A1).
Regarding claim 20, modified McNeely teaches the system of claim 1. McNeely has been modified with West to include the holder and illuminator, where [0032] of West describes that the illuminators typically include light emitting diodes. However, McNeely nor West describe an optical diffuser positioned between said light source and a viewing surface.
In the same problem solving area of illuminating a microfluidic array through the use of one or more light emitting diodes, Yoder teaches that a light shaping diffuser may be placed on the output end of a light emitting diode to shape the light and provide better illumination uniformity (Yoder; [0139], [0140]).
It would have been obvious to one skilled in the art to modify the illuminator of modified McNeely such that it further includes a light shaping diffuser on its output end as taught by Yoder because Yoder teaches that the diffuser allows for better illumination uniformity (Yoder; [0140]).
Other References Cited
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Levner (US-2018/0320125-A1) teaches a clamping device 570 that includes a platform 585 for engaging the bottom side of a microfluidic device 500, a plurality of elongated posts 590 that extend upwardly from platform 585, a compression plate 580, and springs 595 connected to the compression plate 580 such that the compressive forces create a substantially uniform pressure on the top side of the microfluidic device 500 (Levner; [0145], Figure 5E).
Buermann (US-2020/0063201-A1) teaches where a flow cell 101 is aligned with objective 110 via rigid body 100, where the flow cell 101 is maintained in contact with reference surface 117 by a preload that applies positive pressure to the side of the flow cell, the preload is formed by compression foot 102 that contacts the flow cell 101 under force of spring 103 (Buermann; [0045], Figures 2A-B).
Bertone (US-2014/0301911-A1) teaches a microfluidic assembly that includes a microfluidic separation device and a support body that receives the microfluidic separation device, the support body configured to apply a substantially distributed compressive preload to the substrate of the planar microfluidic separation device (Bertone; abstract). [0045] describe the use of fasteners 166 (nuts 166a and bolts 166b) for applying the compressive preload.
Romig (US-2023/0278039-A1) teaches a sealing mechanism that provides a sealing force to a cover plate, where the sealing mechanism may comprise at least one biasing element configured to provide the sealing force to hold the cover in the sealing position (Romig; [0073], [0075], Figures 3A-B).
Conclusion
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/S.Y.L./Examiner, Art Unit 1796
/MELVIN C. MAYES/Supervisory Patent Examiner, Art Unit 1759
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