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 .
Examiner Note
In view of the amendments and applicant's remarks filed on 11/21/2025 page 6 has been considered and are persuasive thereby drawing objection are hereby withdrawn.
Response to Arguments
Applicant's amendment to claims 1, 12, 13 and 17 filed 11/21/2025 has been fully considered but they are not persuasive. Applicant’s amendment to the independent claim significantly changes the scope of the invention as a whole.
Applicant’s arguments have been considered, but are moot in view of the new ground(s) of rejection, necessitated by applicant's amendment, of claim 1 and 17 presented in this Office action.
Further, it is respectfully pointed out that the applied prior art is considered to meet all of applicant’s limitations per rejections below. Most responses to arguments are addressed in rejections below.
While the amendments as presented do not present allowable subject matter, in the interest of compact prosecution, examiner feels that a further interview may help to expedite prosecution of the application. Examiner is available for an interview at Applicant's convenience at the number below should Applicant wish to discuss the case further.
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 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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 1-9, 11-13, 15-26, 62 and 63 are rejected under 35 U.S.C. 103 as being unpatentable over Feng (US PUB 2016/0109693) in view of CHOU et al. (US PUB 2021/0255177; herein after “Chou”), and further in view of Tso et al. (US 6635226).
Regarding claim 1, Feng teaches an apparatus (a confocal imaging system 100, FIG. 1, para. [0050]), comprising: a substrate (a structure 600 and a flow cell 1000, FIGS. 7 and 10A-10B) comprising a pair of plates (e.g., substrates 1010, 1012) and a plurality of spacers (e.g., O-ring 1014) positioned between the plates to define a gap (e.g., a gap 614, FIGS. 6A-7) between the pair of plates (para. [0067] and [0074]); wherein the substrate comprises an inlet and an outlet in fluid communication with the gap (i.e., Two or more tubes (e.g., inlets1612/outlets 1614) are provided with respect to open container 1610, which serve as inlet(s) (3 inlets) and/or outlet(s) thereof, para. [0090], FIGS. 16A and 16B); and an imaging system (e.g., a TDI image sensor 146), wherein a portion of a sample (a tissue sample 120) is to be received within the gap of the substrate (as shown at least in FIGS. 1 and 10B, para. [0051]-[0052]) and the imaging system is to obtain image data of the portion of the sample (i.e., TDI image sensor 146 is a long linear sensor, such as 3200×64 pixel sensor, for capturing high resolution images (e.g., acquire image data) of tissue sample 120, para. 0055]), the image data to be used to determine a concentration of the portion of the sample (i.e., imaging can be carried out as part of a nucleic acid detection technique and/or to determine the shape or form of the tissue sample (e.g., a concentration of the sample), para. [0089]).
Feng teaches all limitations except for explicit teaching of spacers, and to determine a concentration of the portion of the sample.
However, in a related field of endeavor Chou teaches the device for the immunoassay comprises a first plate and a second plate. Conventional glass slide was used as the first plate and an X-plate with a 10 μm spacer was used as the second plate, as shown in FIG. 4, para. [0121].
The sample is imaged, and the images are analyzed to measure the concentration of a target analyte, para. [0077]-[0080].
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device of Feng such that the device having spacers between plates, as shown in FIG. 4, and the sample is imaged, and the images are analyzed to measure the concentration of a target analyte as taught by Chou, for the purpose of reduction in binding time of analyte or entity, detection of analytes, quantify of a volume, quantify of a concentration, mixing of reagents, or control of a concentration (analytes, entity or reagents).
Feng fails to teach the outlet opening downwardly to waste.
In a related field of endeavor Tso teaches a microanalytical device 11 (GIG. 1) comprising substrate 13 having a substantially planar surface 15 containing a reaction zone 17 in the form of a shallow cavity, i.e., a cavity having a depth of micron or even submicron dimensions. A cover plate 21 is shown arranged over with substrate 13… Fluid, e.g., sample to be analyzed, analytical reagents, reactants or the like, are introduced into the reaction chamber from an external source through inlet port 27; outlet port 29 enables passage of fluid from the reaction chamber to an external receptacle. Accordingly, "closure" of the device by aligning the cover with the substrate and forming a seal therebetween results in formation of a reaction chamber into which fluids may be introduced through inlet port 27 and removed through outlet port 29, column 8, lines 33-54, also see in a related embodiment of the invention, as illustrated in FIG. 2, column 8, line 60 to column 9, line 31.
Referring to FIG. 28, this particular configuration provides a mixing chamber 628 which is formed from the intersection of the downstream terminus 612 of the separation microcolumn, the aperture 622 (which comprises a mixing chamber inlet means), and the outlet port 616. The outlet port 616 may optionally be tapered to provide an outlet nozzle. Droplets, containing a mixture of sample eluate and makeup fluid, are generated and expelled from the mixing chamber and may be collected using known techniques, column 28, lines 56-65.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device of Feng such that an outlet port may optionally be tapered (downwardly to waste) to provide an outlet nozzle as taught by Tso for the purpose of allowing fluid communication between the fluid conducting compartment and the separation microcolumn, a number of separation or detection enhancing operations may be conducted during the course of fluid flow (see column 15, lines 1-8).
Regarding claim 13, Feng as set forth in claim 1 above further teaches a method (a method 1100, FIG. 11, para. [0075]), comprising: dispensing a sample (120) onto a first plate (1010) of a substrate (1000) (see steps 110 and 1115, para. [0076]-[0077]); positioning a second plate (1012) of the substrate on the first plate and defining a gap (1020) between the first plate and the second plate using a plurality of spacers (1014) (see step 1120, para. [0078] and [0074]); obtaining image data of the sample (step 1125, para. [0079], and i.e., imaging steps that accompany a sequencing or other nucleic acid detection technique, para. [0080], also see para. [0055]); and determining a concentration of the sample using the image data (i.e., imaging can be carried out as part of a nucleic acid detection technique and/or to determine the shape or form of the tissue sample (e.g., a concentration of the sample), para. [0089]).
Feng teaches all limitations except for explicit teaching of spacers, and to determine a concentration of the portion of the sample.
However, in a related field of endeavor Chou teaches the device for the immunoassay comprises a first plate and a second plate. Conventional glass slide was used as the first plate and an X-plate with a 10 μm spacer was used as the second plate, as shown in FIG. 4, para. [0121].
The sample is imaged, and the images are analyzed to measure the concentration of a target analyte, para. [0077]-[0080].
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device of Feng such that the device having spacers between plates, as shown in FIG. 4, and the sample is imaged, and the images are analyzed to measure the concentration of a target analyte as taught by Chou, for the purpose of reduction in binding time of analyte or entity, detection of analytes, quantify of a volume, quantify of a concentration, mixing of reagents, or control of a concentration (analytes, entity or reagents).
Feng fails to teach the spacers comprise ball bearings having opposing flat surfaces.
However, in a related field of endeavor Chou teaches the spacers that are used to regulate the sample or a relevant volume of the sample are replaced by (a) positioning sensors that can measure the plate inner spacing, and (b) the devices that can control the plate positions and move the plates into a desired plate inner spacing (via ball bearings) based on the information provided the sensors. In some embodiment, all the spacers are replaced by translation stage (e.g., ball bearings), monitoring sensors and feedback system, para. [0182].
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device of Feng such that the devices that can control the plate positions by translation stage (e.g., ball bearings), monitoring sensors and feedback system as taught by Chou, for the purpose of enhancing the movement of the plates into a desired plate inner spacing.
Regarding claim 2, Feng fails to teach the spacers comprise ball bearings having opposing flat surfaces.
However, in a related field of endeavor Chou teaches the spacers that are used to regulate the sample or a relevant volume of the sample are replaced by (a) positioning sensors that can measure the plate inner spacing, and (b) the devices that can control the plate positions and move the plates into a desired plate inner spacing (via ball bearings) based on the information provided the sensors. In some embodiment, all the spacers are replaced by translation stage (e.g., ball bearings), monitoring sensors and feedback system, para. [0182].
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device of Feng such that the devices that can control the plate positions by translation stage (e.g., ball bearings), monitoring sensors and feedback system as taught by Chou, for the purpose of enhancing the movement of the plates into a desired plate inner spacing.
Regarding claims 3 and 15, Feng fails to teach the plurality of spacers comprises three spacers.
However, in a related field of endeavor Chou teaches the device for the immunoassay comprises a first plate and a second plate. Conventional glass slide was used as the first plate and an X-plate with a 10 μm spacer was used as the second plate, as shown in FIG. 4, para. [0121].
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device of Feng such that the device having three spacers between plates, as shown in FIG. 4, as taught by Chou, for the purpose of reduction in binding and accommodate multiple sample compartments.
Regarding claim 4, Feng fails to teach the gap is about 500 micrometers.
However, in a related field of endeavor Chou teaches the spacer height of the spacing between the plates, and/or sample thickness is between 150 µm to 200 µm, para. [0069].
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device of Feng such that the spacing between the plates is between 150 µm to 200 µm, as taught by Chou, for the purpose of having an uniform thickness of the layer is confined by the inner surfaces of the plates and is regulated by the plates and the spacers.
Furthermore, it has held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges such as gap of about 500 µm involves only routine skill in the art. In re Aller, 105 USPQ 233.
Regarding claim 5, Feng according to claim 1 further teaches a channel (1020) is defined between the pair of plates (as shown at least in FIG. 10B).
Regarding claim 6, Feng according to claim 1 further teaches the substrate further comprises a seal (O-ring 1014) positioned between the pair of plates and defines the channel (as shown in FIGS. 10A-10B).
Regarding claim 7, Feng according to claim 1 further teaches the seal (1014) is positioned around a perimeter of the pair of plates (as shown in FIG. 10A).
Regarding claim 8, Feng according to claim 1 further teaches the substrate comprises a mask (e.g., an adhesive layer 1214 (a mask), as shown in FIGS. 14A and 14B, para. [0084]).
Regarding claim 9, Feng according to claim 8 further teaches the mask is an opaque mask (e.g., an adhesive layer 1214 (an opaque mask), as shown in FIGS. 14A and 14B).
Regarding claim 11, Feng fails to teach the substrate comprises a plurality of channels.
However, in a related field of endeavor Chou teaches a first plate, a second plate, and spacers, where one or both of the plates comprise, inside the sample contact area, one or more spacers of predetermined substantially uniform height; and one or both of the plates comprise, on the respective inner surface, a plurality of separated particles, see para. [0017] to [0023].
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device of Feng such that a first plate, a second plate, and spacers creates a plurality of separated chambers/channels, as shown in FIG. 4B, as taught by Chou, for the purpose of having the inner surfaces of the plates and is regulated by the plates and the spacers.
Regarding claim 12, Feng according to claim 1 further teaches the inlet comprises a first inlet (1612), and the substrate further comprises a second inlet and a third inlet in fluid communication with the gap (1620) (i.e., Two or more tubes (e.g., second and third inlets1612/outlets 1614) are provided with respect to open container 1610, which serve as inlet(s) (3 inlets) and/or outlet(s) thereof, para. [0090], FIGS. 16A and 16B).
Regarding claim 16, Feng according to claim 13 further teaches positioning a seal (1014) around a perimeter of the first plate and the second plate (as shown in FIGS. 10A).
Regarding claim 17, Feng as set forth in claim 13 above further teaches a method (a method 1100, FIG. 11, para. [0075]), comprising: dispensing a sample (120) in an inlet (1022) of a channel (e.g., chamber 1020) of a substrate (1000) (see steps 1110, 1115, 1120 and 1125, para. [0076]-[0079], also see para. [0074], and as shown in FIGS. 1A-10B); obtaining image data of the sample (i.e., imaging steps that accompany a sequencing or other nucleic acid detection technique, para. [0080], also see para. [0055]); determining a concentration of the sample using the image data (i.e., imaging can be carried out as part of a nucleic acid detection technique and/or to determine the shape or form of the tissue sample (e.g., a concentration of the sample), para. [0089]).
Feng teaches all limitations except for explicit teaching of determine a concentration of the portion of the sample.
However, in a related field of endeavor Chou teaches the sample is imaged, and the images are analyzed to measure the concentration of a target analyte, para. [0077]-[0080].
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device of Feng such that the sample is imaged, and the images are analyzed to measure the concentration of a target analyte as taught by Chou, for the purpose of reduction in binding time of analyte or entity, detection of analytes, quantify of a volume, quantify of a concentration, mixing of reagents, or control of a concentration (analytes, entity or reagents).
Feng fails to teach flowing the sample downwardly out of an outlet of the channel to waste.
In a related field of endeavor Tso teaches a microanalytical device 11 (GIG. 1) comprising substrate 13 having a substantially planar surface 15 containing a reaction zone 17 in the form of a shallow cavity, i.e., a cavity having a depth of micron or even submicron dimensions. A cover plate 21 is shown arranged over with substrate 13… Fluid, e.g., sample to be analyzed, analytical reagents, reactants or the like, are introduced into the reaction chamber from an external source through inlet port 27; outlet port 29 enables passage of fluid from the reaction chamber to an external receptacle. Accordingly, "closure" of the device by aligning the cover with the substrate and forming a seal therebetween results in formation of a reaction chamber into which fluids may be introduced through inlet port 27 and removed through outlet port 29, column 8, lines 33-54, also see in a related embodiment of the invention, as illustrated in FIG. 2, column 8, line 60 to column 9, line 31.
Referring to FIG. 28, this particular configuration provides a mixing chamber 628 which is formed from the intersection of the downstream terminus 612 of the separation microcolumn, the aperture 622 (which comprises a mixing chamber inlet means), and the outlet port 616. The outlet port 616 may optionally be tapered to provide an outlet nozzle. Droplets, containing a mixture of sample eluate and makeup fluid, are generated and expelled from the mixing chamber and may be collected using known techniques, column 28, lines 56-65.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device of Feng such that an outlet port may optionally be tapered (downwardly to waste) to provide an outlet nozzle as taught by Tso for the purpose of allowing fluid communication between the fluid conducting compartment and the separation microcolumn, a number of separation or detection enhancing operations may be conducted during the course of fluid flow (see column 15, lines 1-8).
Regarding claim 18, Feng according to claim 17 further teaches obtaining the image data comprises obtaining the image data through a window of the substrate (i.e., imaging is performed through top substrate 612 (window of the substrate 600), as shown in FIG. 7, para. [0068]).
Regarding claim 19, Feng according to claim 18 further teaches the window comprises an unmasked region (i.e., a lens focusing beam 620 passes through an unmasked region of the substrate 600/612, as shown in FIG. 7) and wherein a masked region (1214) may surround the unmasked region (1230) (as shown in FIG. 14A, para. [0084]).
Regarding claim 20, Feng according to claim 17 further teaches dispensing a fluid into the channel to separate the sample and another sample (i.e., an integrated system can include separate fluidic systems (sample) to carry out amplification methods and to carry out detection methods, para. [0046]).
Regarding claim 21, Feng according to claim 20 further teaches the fluid comprises oil (i.e., FIGS. 17A and 17B, a liquid-immersion (e.g., immersion oil) imaging process can be used, para. [0092]).
Regarding claim 22, Feng according to claim 20 further teaches dispensing the fluid into the channel comprises dispensing the fluid into a second inlet of the channel (i.e., Two or more tubes (e.g., second inlet) are provided with respect to open container 1610, which serve as inlet(s) (2nd inlet), para. [0090], FIGS. 16A and 16B).
Regarding claim 23, Feng according to claim 17 further teaches flowing the sample out of the outlet (1024/1614) of the channel comprises urging the sample out of the outlet of the channel using negative pressure (i.e., Referring now to FIG. 16B, upon completion of the chemistry operations, using tube 1612 and tube 1614, open container 1610 is substantially drained of liquid 1620 (e.g., the system comprising components such as pumps having negative pressure), para. [0046] and [0091], also see para. [0079]).
Regarding claim 24, Feng according to claim 17 further teaches flowing the sample out of the outlet of the channel comprises urging the sample out of the outlet of the channel using a fluid (i.e., Referring now to FIG. 16B, upon completion of the chemistry operations, using tube 1612 and tube 1614, open container 1610 is substantially drained of liquid 1620 (e.g., the system comprising components such as pumps), para. [0046] and [0091], also see para. [0079]).
Regarding claim 25, Feng as set forth in claim 1 above further teaches apparatus (a confocal imaging system 100, FIG. 1, para. [0050]), comprising: a substrate (a structure 600 and a flow cell 1000, FIGS. 7 and 10A-10B), comprising: a channel (e.g., chamber 1020) including an inlet (1022) and an outlet (1024) (para. [0074]); and a valve disposed between the inlet and the outlet, wherein the channel comprises a first portion between the valve and the inlet and a second portion between the valve and the outlet (i.e., the system comprising components such as pumps, valves (to separate inlet and outlet into 1st and 2nd portions), reservoirs, fluidic lines and the like, para. [0046]); and an imaging system (e.g., a TDI image sensor 146), wherein a portion of a sample is to be received within the first portion of the channel of the substrate and the imaging system is to obtain image data of the portion of the sample (i.e., TDI image sensor 146 is a long linear sensor, such as 3200×64 pixel sensor, for capturing high resolution images (e.g., acquire image data) of tissue sample 120, para. 0055]), the image data to be used to determine a concentration of the portion of the sample (i.e., imaging can be carried out as part of a nucleic acid detection technique and/or to determine the shape or form of the tissue sample (e.g., a concentration of the sample), para. [0089]).
Feng teaches all limitations except for explicit teaching of spacers, and to determine a concentration of the portion of the sample.
However, in a related field of endeavor Chou teaches the sample is imaged, and the images are analyzed to measure the concentration of a target analyte, para. [0077]-[0080].
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device of Feng such that the sample is imaged, and the images are analyzed to measure the concentration of a target analyte as taught by Chou, for the purpose of reduction in binding time of analyte or entity, detection of analytes, quantify of a volume, quantify of a concentration, mixing of reagents, or control of a concentration (analytes, entity or reagents).
Regarding claim 26, Feng according to claim 25 further teaches a pump to move the sample from the inlet to the outlet (e.g., the system comprising components such as pumps, para. [0046]).
Regarding claim 62, Feng according to claim 1 further teaches a centrifugal pump to move the sample from the inlet to the outlet (e.g., the system comprising components such as pumps, valves, reservoirs, fluidic lines and the like (e.g., a centrifugal pump), para. [0046]).
Regarding claim 63, Feng according to claim 9 further teaches one of the pair of plates comprises the opaque mask (e.g., an adhesive layer 1214 (an opaque mask), as shown in FIGS. 14A and 14B) and the opaque mask defines a window through which the imaging system is to obtain the image data of the portion of the sample (i.e., aperture plate 132 and aperture plate 136 can be formed of a glass substrate (e.g., plates) coated by patterned opaque layers (e.g., the opaque mask defines a window), such as chrome. Further, the height and length of aperture plate 132 and aperture plate 136 may depend on the overall size of TDI image sensor 146 (e.g., to obtain the image data), see para. [0057], as shown in FOG. 3).
Allowable Subject Matter
Claims 27-29 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter:
Regarding claim 27, the prior art does not teach, or renders obvious, regarding a pump comprises a plate comprising an axis of rotation and an actuator to rotate the plate, the substrate coupled to the plate and extending radially from the axis of rotation.
Claims 28 and 29 depend upon allowable claim 27.
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 extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MUSTAK CHOUDHURY whose telephone number is (571)272-5247. The examiner can normally be reached on M-F 8AM-5PM EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ricky Mack can be reached on 5712722333. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MUSTAK CHOUDHURY/Primary Examiner, Art Unit 2872
February 23, 2026