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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 8/15/24 is being considered by the examiner.
Claim Status
Claims 1-19 are pending and are examined.
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.
Claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 13, 14, 16, 17, and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Vladesavljevic (“Production of liposomes of microengineered membrane and co-flow microfluidic device.” Colloids and Surfaces A. 458:168-177. 2014.) in view of Tian ("Microfluidic co-flow of Newtonian and viscoelastic fluids for high-resolution separation of microparticles." Lab Chip. 17(18). 3078-3085. 2017).
Regarding Claim 1, Vladesavljevic teaches a device for reducing a parabolic velocity profile (See 3.2 Microfluidic vescicle formation. a parabolic velocity profile), comprising:
a coflow generator configured to provide a buffer solution and a reaction mixture of at least two components to form a coflow pattern in a tubing (See 2.3. Co-flow microfluidic device. Fig. 3. Microfluidic co-flow device consisted of coaxial assembly of glass capillaries. Both capillaries were glued onto a microscope slide and two needles (O.D. 0.9 mm) were glued onto the slide such that the entrances to each capillary were situated inside the hubs (Fig. 3a)); and
wherein the tubing is configured to receive the reaction mixture and the buffer solution from the flow generator and flow the reaction mixture bounded by the buffer solution without contacting a wall of the tubing (See 2.3. Co-flow microfluidic device. A PTFE tubing (I.D. 0.80 mm) was used to deliver the organic phase to the inner capillary, while a PE tubing was used to deliver the aqueous phase to the square capillary. Another PTFE tubing (I.D. 1.5 mm) was attached to the outlet of the square capillary to transfer the liposomal solution into a vial.).
Vladesavljevic is silent to a coflow separator configured to separate the buffer solution from the reaction mixture, wherein the coflow generator and the coflow separator are coupled through the tubing.
Tian teaches in the related art of microfluidic co-flow. Fig. 1a. (a) Schematic of the microfluidic device for particle separation using a co-flow of viscoelastic and Newtonian media. The microchannel consists of two inlets for the sample fluid (Newtonian fluid) and sheath fluid (viscoelastic fluid), one straight separation channel with a rectangular cross-section (50 μm high and 20 μm wide), and five outlets for the collection of large and small particles.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have added a coflow separator configured to separate the buffer solution from the reaction mixture, wherein the coflow generator and the coflow separator are coupled through the tubing, as taught by Tian, in the device of Vladesavljevic, to allow for high-resolution approach for the efficient separation of small microparticles, as taught by Tian, in the Introduction, last sentence.
Regarding Claim 2, modified Vladisavljevic the device of claim 1, wherein the coflow generator is configured to flow the buffer solution adjacent to the wall of the tubing (See 2.3. Co-flow microfluidic device. Fig. 3. Microfluidic co-flow device consisted of coaxial assembly of glass capillaries. Both capillaries were glued onto a microscope slide and two needles (O.D. 0.9 mm) were glued onto the slide such that the entrances to each capillary were situated inside the hubs (Fig. 3a)).
Regarding Claim 3, modified Vladisavljevic teaches the device of claim 1, wherein the reaction mixture and the buffer solution flow in a laminar state in the tubing by controlling a flow rate of the mixture or the buffer solution (the examiner notes that the reaction mixture and the buffer solution flow are directed to intended use of the device. The reaction mixture and buffer solution are not positively recited and are not part of the claimed device).
Regarding Claim 4, modified Vladisavljevic teaches the device of claim 1, wherein a ratio between a flow rate of the buffer solution and a flow rate of the reaction mixture ranges from about 1:1 to about 10:1 (the examiner notes this limitation is directed to intended use of the device. The buffer solution is not positively recited and is not part of the claimed device. Therefore, the flow rates are directed to intended use of the device).
Regarding Claim 5, modified Vladisavljevic teaches the device of claim 3, wherein the flow rate of the buffer solution ranges from 3 μL/s to about 60 μL/s, and the flow rate of the reaction mixture ranges from about 3 μL/s to about 6 μL/s (the examiner notes this limitation is directed to intended use of the device. The buffer solution is not positively recited and is not part of the claimed device. Therefore, the flow rates are directed to intended use of the device).
Regarding Claim 6, modified Vladisavljevic teaches the device of claim 1, wherein the buffer solution is guided to be on a periphery of the tubing and concentric to the reaction mixture (the examiner notes this limitation is directed to intended use of the device. The buffer solution is not positive recited and is not part of the claimed device).
Regarding Claim 7, modified Vladisavljevic teaches the device of claim 1, wherein the device is configured to complete a reaction of the reaction mixture in a predetermined time, wherein the predetermined time is less than 1000 ms (the device is capable of being configured to complete a reaction in a predetermined time).
Regarding Claim 8, modified Vladisavljevic teaches the device of claim 1, wherein the tubing comprises a capillary tubing, a three-dimensional (3D)-printed tubing, a polyether ether ketone (PEEK) tubing, a 3D-printed IP-S tubing, or a 3D IP-Q tubing (See section 2.3 co-flow microfluidic device. A PTFE tubing (I.D. 0.80 mm) was used to deliver the organic phase to the inner capillary, while a PE tubing was used to deliver the aqueous phase to the square capillary. Another PTFE tubing (I.D. 1.5 mm) was attached to the outlet of the square capillary to transfer the liposomal solution into a vial.).
Regarding Claim 9, modified Vladisavljevic teaches the device of claim 1, wherein the coflow separator comprises an outlet for a release of the buffer solution (See Section 2.2 Membrane dispersion devices. The cross flow module (Fig. 2b) contained a flat membrane with 4 separate active regions. Tian teaches (a) Schematic of the microfluidic device for particle separation using a co-flow of viscoelastic and Newtonian media. The microchannel consists of two inlets for the sample fluid (Newtonian fluid) and sheath fluid (viscoelastic fluid), one straight separation channel with a rectangular cross-section (50 μm high and 20 μm wide), and five outlets for the collection of large and small particles.).
Regarding Claim 13, modified Vladisavljevic teaches the device of claim 1, wherein the device is a chip assembly (Materials and methods. Device design and fabrication. The molded PDMS slab was bonded to a glass substrate).
Regarding Claim 14, modified Vladisavljevic teaches a method for reducing a parabolic velocity profile (See 3.2 Microfluidic vescicle formation. a parabolic velocity profile), comprising
providing a buffer solution to a coflow generator; providing a reaction mixture of at least two components to the coflow generator; flowing the buffer solution adjacent to an inner wall of a tubing; flowing the reaction mixture bounded by the buffer solution without contacting the inner wall of the tubing (See 2.3. Co-flow microfluidic device. Fig. 3. Microfluidic co-flow device consisted of coaxial assembly of glass capillaries. Both capillaries were glued onto a microscope slide and two needles (O.D. 0.9 mm) were glued onto the slide such that the entrances to each capillary were situated inside the hubs (Fig. 3a)); and
Vladesavljevic is silent to purging the buffer solution at the end of the tubing using a coflow separator.
Tian teaches in the related art of microfluidic co-flow. Fig. 1a. (a) Schematic of the microfluidic device for particle separation using a co-flow of viscoelastic and Newtonian media. The microchannel consists of two inlets for the sample fluid (Newtonian fluid) and sheath fluid (viscoelastic fluid), one straight separation channel with a rectangular cross-section (50 μm high and 20 μm wide), and five outlets for the collection of large and small particles.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have added a coflow separator configured to separate the buffer solution from the reaction mixture, wherein the coflow generator and the coflow separator are coupled through the tubing, as taught by Tian, in the device of Vladesavljevic, to allow for high-resolution approach for the efficient separation of small microparticles, as taught by Tian, in the Introduction, last sentence.
Regarding Claim 16, modified Vladisavljevic teaches the method of claim 14, further comprising adjusting a flow rate of the buffer solution, the reaction mixture, or a combination thereof (The sheath and sample fluids were separately injected into the microchannel using two syringe pumps. The flow rates were precisely adjusted to pinch the sample fluid into narrow streams along the sidewalls.).
Regarding Claim 17, modified Vladisavljevic teaches the method of claim 14, further comprising adjusting a width of the buffer solution in the tubing to absorb a steepest part of a parabolic velocity distribution of the mixture, wherein the width is a distance from the inner wall of the tubing to a boundary between the buffer solution and the reaction mixture (Fig. 5 shows the velocity field within the device with an orifice diameter of 209 μm. As expected, the maximum velocity was reached in the centre of the orifice. The organic phase velocity dropped significantly downstream of the orifice compared to the average velocity in the orifice, due to increase in the cross-sectional area and the drag force from the surrounding water phase, because the water phase velocity was lower than that of the organic phase. At Qo = Qw = 0.6 ml h−1, the steady-state velocity profile was established within the distance of 2 nozzle diameters from the nozzle. At Qo = 0.6 ml h−1 and Qw = 9 ml h−1, the steady state parabolic velocity profile was established farther downstream, as can be seen from Fig. 6. For the conditions specified in Fig. 6, at a distance of L = 0.5D and L = D downstream of the orifice, fluid flow exhibits two velocity maxima, corresponding to the maximum velocities in the two phases, and a minimum in between, corresponding to the position of the orifice wall. At L = 2D, the velocity profile was not yet fully developed with a constant velocity in the central part of the collection tube and a sudden drop near the tube wall. At L = 12D, a parabolic velocity profile was established over the whole cross section of the tube, as expected for laminar flow conditions.).
Regarding Claim 18, modified Vladisavljevic teaches the method of claim 14, further comprising generating a droplet of the reaction mixture at a predetermined gas pressure (See Fig. 1, droplets).
Claims 10-12 are rejected under 35 U.S.C. 103 as being unpatentable over Vladesavljevic (“Production of liposomes of microengineered membrane and co-flow microfluidic device.” Colloids and Surfaces A. 458:168-177. 2014.), in view of Tian ("Microfluidic co-flow of Newtonian and viscoelastic fluids for high-resolution separation of microparticles." Lab Chip. 17(18). 3078-3085. 2017), and further in view of Turk (US Pub 2016/0311682).
Regarding Claims 10-12, modified Vladisavljevic teaches the device of claim 1.
Turk is silent to a micro sprayer configured to generate a droplet of the reaction mixture, wherein the sprayer is coupled to the flow separator, the micro sprayer comprises a gas inlet for providing gas pressure, and the tubing is aligned and centered in a center of the flow separator and the micro sprayer.
Turk teaches [0136] Fig 10 the nozzle 1012 is positioned such that the spray 1024 is generally directed from the nozzle 1012 in a counter-flow relation to the direction of gas flow 1028 through the gas conduit 1008. Alternatively, the nozzle 1012 may be positioned such that the spray 1024 is generally directed from the nozzle 1012 in a co-flow relation to the direction of gas flow 1028 (in the same direction as the gas flow 1028) or in a cross-flow relation to the direction of gas flow 1028.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have added a micro sprayer configured to generate a droplet of the reaction mixture, wherein the sprayer is coupled to the flow separator, the micro sprayer comprises a gas inlet for providing gas pressure, and the tubing is aligned and centered in a center of the flow separator and the micro sprayer, as taught by Turk, in the device of modified Vladisavljevic, to allow for treating or purifying a gas stream, as taught by Turk, in [0002].
Claims 15 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Vladesavljevic (“Production of liposomes of microengineered membrane and co-flow microfluidic device.” Colloids and Surfaces A. 458:168-177. 2014.), in view of Tian ("Microfluidic co-flow of Newtonian and viscoelastic fluids for high-resolution separation of microparticles." Lab Chip. 17(18). 3078-3085. 2017), in view of Yantz (US Pub 2012/0045826).
Regarding Claims 15 and 19, modified Vladisavljevic teaches the method of claim 14.
Modified Vladisavljevic is silent to adjusting a temperature of the buffer solution or the reaction mixture and the the coflow generator and the coflow separator are produced by a three-dimensional printer.
Yantz teaches in the related art of fluidics. [0233] temperatures and times can be adjusted, and various reagents, in addition to those listed above, can undergo similar treatments. [0286] The structure of the device (FIG. 5C) integrates sample inlet, fluid flow channels, reaction and imaging wells, and venting into a single fabricated component. Some of the modules illustrated are fabricated by rapid prototyping techniques. Parts illustrated in FIG. 5C and FIG. 5D were fabricated using a Polyjet 3D printer,
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have added the steps of adjusting a temperature of the buffer solution or the reaction mixture and producing the the coflow generator and the coflow separator by a three-dimensional printer, as taught by Yantz, in the method, as taught by Modified Vladisavljevic, to allow for rapid, accurate, and quantitative, easy-to-use, and cost-effective tests, as taught by Yantz, in the Abstract.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JACQUELINE BRAZIN whose telephone number is (571)270-1457. The examiner can normally be reached M-F 8-5.
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/JB/
/CHARLES CAPOZZI/Supervisory Patent Examiner, Art Unit 1798
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