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 .
Claim Status
Claims 1, 3-10, and 15 are pending.
Claims 1, 10, and 15 have been amended.
Claim 2 has been canceled.
Claims 11-14 have been withdrawn.
Drawings
The drawings are objected to under 37 CFR 1.83(a). The drawings must show every feature of the invention specified in the claims. Therefore the microfluidic channel must be shown or the feature(s) canceled from the claim(s). No new matter should be entered.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1, 2, 4, 7, 8, 10, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Stephenson et. al. (WO 2019023159 A1) in view of Winger (US 9513253 B2) and Selden et. al. (KR 20190111165A).
Regarding claim 1 Stephenson teaches ”A microfluidic magnetic microbead interaction device comprising:” (Para [0014], a device, wherein each droplet of the plurality of droplets comprises a first fluid with a plurality of magnetic particles. The device includes a microchannel); “a body having” (Fig. 2, and Para [0095], This partitioning immediately precedes splitting of the droplet at a fork leading to two outlet channels, outlet 1 (branch 817) and outlet 2 (branch 818). Frame 4 (FIG. 8D); “a microfluidic interior” (Para [0002], Microfluidic devices which include one or more microchannels); “and a port connected to the microfluidic interior;” (Para [0085], Immediately after, small copper wire is placed into the still molten electrode ports to provide attachments to electronic power supply. Electrode copper wire connections can be stabilized using an epoxy overlay to minimize breakage of the wire. Other implementations of the electrode configuration exist, including pre-fabricating electrodes on the substrate and aligning the microfluidic channels to these existing electrodes.); “ferromagnetic microbeads within the microfluidic interior;” (Paras [0060] and [0069], superparamagnetic particles which are characterized by a strong ferromagnetic coupling into domains of a limited size. The narrow slanted supply channel 272 depicted was found to be advantageous for smaller superparamagnetic microparticles); “a magnet” (Abstract, A first magnet introduces). The recitation “configured to exert a magnetic force on the ferromagnetic microbeads to attract the ferromagnetic microbeads to a region of the microfluidic interior” is capability of the magnet. Stephenson discloses the positively claimed structural elements of the magnet as claimed, such magnet is said to be fully capable of the recited adaption in as much as recited and required herein.
Stephenson teaches a heater within (Para [0085), however that is for the production of the device. Therefore Stephenson does not explicitly teach “a heater to heat fluid in the region to a temperature above a Curie temperature”.
Winger teaches droplet actuators and techniques in addition to having a magnetic responsive and having magnetic bead. Winger also teaches “a heater” (Column 30 lines 36-42, Column 30 lines 43-61, Heating devices 1025 for controlling the temperature within, for example, certain reaction and/or washing zones of droplet actuator 1005. In one example, heating devices 1025 may be heater bars that are positioned in relation to droplet actuator 1005 for providing thermal control thereof.). The recitation “configured to heat fluid in the region to a temperature above a Curie temperature” is capability of the heater however taught within (Column 30 lines 43-61 of Winger in that the heating devices control temperature within the reaction, washing and droplet zones. In addition to Stephenson teachings of the Curie temperature within( Para [0060], Some materials show induced magnetic behavior that follows a Curie type law but with exceptionally large values for the Curie constants).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Stephenson to incorporate the teachings of Winger a heater. Adding a heater to the device accelerates the reaction process and provides for a device capable of reactions which require temperature regulation.
Further taught by Stephenson “ the ferromagnetic microbeads;” (Para [0060]and [0016], Each magnetic particle of the plurality of magnetic particles is a paramagnetic particle or a superparamagnetic particle. While nanoparticles are smaller than 0.5 micron in diameter (typically 5-500 nm), the larger microbeads are 0.5-500 microns in diameter. An advantage of superparamagnetic particles is that they respond more strongly to the externally applied magnetic field and move faster to the inducing magnet. They are characterized by a strong ferromagnetic or ferrimagnetic type of coupling into domains of a limited size that behave independently from one another. ); “ a mixer” (Para [0046], different fluids have likely mixed via diffusion or advection (mechanically driven flow) or convection (thermal driven flow), or some combination.). The recitation “ configured to mix fluids and the ferromagnetic microbeads while the fluid is at the temperature.” is capability of the mixer. Stephenson discloses the positively claimed structural elements of the mixer as claimed, such mixers are said to be fully capable of the recited adaption in as much as recited and required herein.
Stephenson does teach a controller within (Para [0119], other specialized components to aid in performing the inventive functions described herein include one or more field programmable gate arrays (FPGA) (not shown), one or more controllers (not shown), or one or more other special-purpose computer chips.) In addition to “computer-readable instructions stored in a non-transitory computer-readable medium (Para [0018] and [0107], one or more computer-readable media including one or more sequences of instructions. The computer-readable medium and the one or more sequences of instructions.
Stephenson does not explicitly teach outputting control signals to the heater causing the heater to heat the fluid to the temperature above the Curie temperature of the ferromagnetic microbeads, or outputting control signals to the mixer to mix the fluid and ferromagnetic microbeads while the fluid is at the temperature above the Curie temperature of the ferromagnetic microbeads”.
However, Winger teaches “and a controller configured to output control signals to the heater causing the heater to heat the fluid” (Column 30 lines 36-42, Column 30 lines 43-61, A controller 1030 of microfluidics system 1000 is electrically coupled to various hardware components of the invention such as heating devices 1025.) Controller 1030 controls the overall operation of microfluidics system 1000. heating devices 1025 for controlling the temperature within, for example, certain reaction and/or washing zones of droplet actuator 1005. In one example, heating devices 1025 may be heater bars that are positioned in relation to droplet actuator 1005 for providing thermal control thereof.)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified Stephenson to incorporate the teachings of Winger wherein the device has a controller configured to output control signals to the heater causing the heater to heat the fluid. Doing so allows the controller to control the setting of the temperature to maintain the needed temperature which is optimal for the process to be conducted on the device. In addition, to increasing the ability to change temperatures fast which is needed for fast thermal cycling.
The recitation “to the temperature above the Curie temperature of the ferromagnetic microbeads” is capability of the heater. Modified Stephenson discloses the positively claimed structural elements of the heater as claimed, such heater are said to be fully capable of the recited adaption in as much as recited and required herein. In addition, Stephenson teaches Curie as already highlighted above.
Further taught by Winger is “and to output control signals to the mixer to mix the fluid and ferromagnetic microbead” (Column 12 lines 8- 15, Column 30 lines 43-61 , Column 13 lines 59-64, A controller 1030 of microfluidics system 1000 is electrically coupled to various hardware components of the invention, such as droplet actuator 1005 any other input and/or output devices (not shown). Controller 1030 controls the overall operation of microfluidics system 1000. “Droplet operation” means any manipulation of a droplet on a droplet actuator. A droplet operation may, for example, include: loading a droplet into the droplet actuator; dispensing one or more droplets from a source droplet; splitting, separating or dividing a droplet into two or more droplets; transporting a droplet from one location to another in any direction; merging or combining two or more droplets into a single droplet; diluting a droplet; mixing a droplet; agitating a droplet; deforming a droplet; retaining a droplet in position; incubating a droplet; heating a droplet; . “Magnetically responsive” means responsive to a magnetic field. “Magnetically responsive beads” include or are composed of magnetically responsive materials. Examples of magnetically responsive materials include paramagnetic materials, ferromagnetic materials, ferrimagnetic materials, and metamagnetic materials. Examples of suitable paramagnetic materials.)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified Stephenson to incorporate the teachings of Winger wherein the and to output control signals to the mixer to mix the fluid and ferromagnetic microbeads. Doing would allow the controller to control the mixing portion to allow the right amount of fluid to be entered at a given time and to allow the flow rate and amounts to be regulated. This control provides for real-time adjustments to be made for optimal mixing within the device.
Stephenson nor Winger teaches heating while mixing as recited within “while the fluid is at the temperature above the Curie temperature of the ferromagnetic microbeads”.
Selden teaches a biochip having a moving mechanism that includes pneumatic, mechanical, magnetic in addition to “while the fluid is at the temperature above the Curie temperature of the ferromagnetic microbeads” within (Page 4, The treatment first prepares the purified DNA and reaction mixture outside the microfluidic plate, places the plate in the controller, primes the plate, loads and mixes reagents over 45 minutes in the plate, and heats for PCR.)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified Stephenson to incorporate the teachings of Selden wherein the controller is configured to mix and heat at the same time. Doing would increases the reaction time and a more uniform mixed component.
Regarding claim 4, modified Stephenson teaches all of claim 1 as above in addition to “wherein the mixer comprises a fluid actuator.” (Para [0046], different fluids have likely mixed via convection (thermal driven flow), or some combination.).
Regarding claim 7, modified Stephenson teaches all of claim 1 in addition to “an ejection orifice extending from the microfluidic interior;” (Fig. 1 and Para [0051], picoinjector 100 includes a microchannel 110); and a fluid actuator to eject portions of the fluid within the microfluidic interior through the ejection orifice. (Para [0018] and [0055], The system operates a pressure actuator to supply a second fluid to the supply channel. The system 200 includes processing system 250, with system operation module 252, and pressure actuators 261 along with a microfluidic device 201. The microfluidic device 201 includes the main microchannel 210, fork 216, microchannel branches 217 and 218, magnets 231 and 232, and picoinjector.).
Regarding claim 8, modified Stephenson teaches all of claim 1 as above in addition to “wherein the microfluidic interior comprises: a microfluidic channel; a mixing loop; and a pump to move the fluid from the microfluidic channel into and through the mixing loop and back to the microfluidic channel.” (Para [0046], The third approach is called droplet wash and split loop. This technique pipes droplets (with magnetic beads each bound to a target) and wash droplets into a channel at a one-to-one correspondence. Then the droplets are electro-coalesced at a junction. The droplets are then split on the device or a different device again. An external magnetic field is used to partition beads to one portion of the droplet prior to splitting. Here the wash efficiency is dependent on the volume ratio between the sample droplet and the wash droplet. Synchronization of the two droplets dictates that the droplets are of similar volume and thus a typical wash efficiency is on the order of 50%. Additionally, the droplets are only split after significant amount of time has passed; thus, the two different fluids have likely mixed via diffusion or advection (mechanically driven flow) or convection (thermal driven flow), or some combination. Further washing can be performed by looping through the procedure again until the desired amount of washing has taken place.). Therefore, the split loop which is for two different fluids to mix via a mechanically driven flow and then looped back through to process again teaches to the microfluidic channel with the mixing loop and the pump (mechanically driven flow) and loops back through.
Regarding claim 9, modified Stephenson teaches all of claim 1 as above in addition to teaching “second ferromagnetic microbeads within the microfluidic interior” (Abstract, Paras [0060] and [0069], superparamagnetic particles which are characterized by a strong ferromagnetic coupling into domains of a limited size. The narrow slanted supply channel 272 depicted was found to be advantageous for smaller superparamagnetic microparticles. A first magnet introduces a magnetic field into the microchannel between the picoinjector and the fork to move magnetic particles in the first droplet toward the first side of the microchannel before the droplet is split at the fork to produce output droplets of the second fluid with magnetic particles.) Therefore the magnetic particles are the ferromagnetic microbeads and two sets of liquids with each having magnetic particles teaches to a second set of ferromagnetic microbeads. Although the recitation “ the second ferromagnetic microbeads having a second Curie temperature different than the Curie temperature of the ferromagnetic microbeads” is capability of the ferromagnetic microbeads its taught within (Para [0060], Some materials show induced magnetic behavior that follows a Cuire type law but with exceptionally large values for the Cuire constants. These materials are known as superparamagnetic. An advantage of superparamagnetic particles is that they respond more strongly to the externally applied magnetic field and move faster to the inducing magnet. They are characterized by a strong ferromagnetic or ferrimagnetic type of coupling into domains of a limited size that behave independently from one another. The bulk properties of such a system resemble that of a paramagnet, but on a microscopic level they are ordered. The materials do show an ordering temperature above which the behavior reverts to ordinary paramagnetism.) The recitation “wherein the heater is to heat the fluid to a second temperature above the second Curie temperature” is capability of the heater which is already taught within claim 1. Further taught “and a recirculation loop in the body, the recirculation loop comprising the microfluidic interior.” (Para [0046], The third approach is called droplet wash and split loop. Further washing can be performed by looping through the procedure again until the desired amount of washing has taken place.). Therefore, loping through the procedure again teaches to the recirculation loop.
Regarding claim 10, modified Stephenson teaches all of claim 1 as above in addition to “wherein the body comprises: a first microfluidic channel ;a second microfluidic channel extending from the first microfluidic channel and forming the microfluidic interior; a third microfluidic channel extending from the microfluidic channel; “(Para [0007] In a first set of embodiments, an apparatus includes a substrate having formed thereon a microchannel (first microfluidic channel), a plurality of microchannel branches comprising a first microchannel (first microfluidic channel) branch and a different second microchannel (second microfluidic channel) branch, and a fork comprising a junction between the microchannel upstream of the fork and the plurality of microchannel branches downstream of the fork. (third microfluidic channel)); “second ferromagnetic microbeads within the third microfluidic channel” (Para [0016], [0060], [0061], and [0066], These materials are known as superparamagnetic. An advantage of superparamagnetic particles is that they respond more strongly to the externally applied magnetic field and move faster to the inducing magnet. They are characterized by a strong ferromagnetic or ferrimagnetic type of coupling into domains of a limited size that behave independently from one another. The portion of the droplet with both fluid B and the magnetic particles is indicated by the close downward diagonal hatching in droplet 293d. By the time the droplet arrives at the fork 216.) The recitation “the second ferromagnetic microbeads having a second Curie temperature” is capability of the ferromagnetic microbeads however taught within (Para [0060], Some materials show induced magnetic behavior that follows a Cuire type law but with exceptionally large values for the Cuire constants. These materials are known as superparamagnetic. An advantage of superparamagnetic particles is that they respond more strongly to the externally applied magnetic field and move faster to the inducing magnet. They are characterized by a strong ferromagnetic or ferrimagnetic type of coupling into domains of a limited size that behave independently from one another. The bulk properties of such a system resemble that of a paramagnet, but on a microscopic level they are ordered. The materials do show an ordering temperature above which the behavior reverts to ordinary paramagnetism.) The recitation “wherein the magnet is to exert a magnetic force on the second ferromagnetic microbeads to attract the second ferromagnetic microbeads to a second region of the microfluidic interior;” is capability of the ferromagnetic microbeads and the magnet. Stephenson discloses the positively claimed structural elements of the ferromagnetic microbeads and the magnet as claimed herein and above, such ferromagnetic microbeads and the magnet are said to be fully capable of the recited adaption in as much as recited and required herein.
However Stephenson does not explicitly teach “a second heater to heat fluid in the second region to a second temperature above the second Curie temperature of the second ferromagnetic microbeads; and a second mixer to mix the fluid within the third microfluidic channel while the fluid is at the second temperature.”.
Winger teaches “a second heater to heat fluid in the second region” (Column 29 lines 67, Column 30 lines 36-42, One or more magnets and one or more heating devices. Additionally, the instrument deck may house one or more heating devices 1025 for controlling the temperature within, for example, certain reaction and/or washing zones of droplet actuator 1005. In one example, heating devices 1025 may be heater bars that are positioned in relation to droplet actuator 1005 for providing thermal control thereof.) Therefore, one or more heating devices used for certain reaction or droplet actuator teach to a second heater to heat a fluid in a second region. The recitation “to a second temperature above the second Curie temperature of the second ferromagnetic microbeads;” is capability of the heater which is already taught within claim 1.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified Stephenson to incorporate the teachings of Winger wherein the a second heater to heat fluid in the second region. Doing so creates a second temperature range which can adjust the temperature as needed to optimize the mixing and interactions within the device.
Winger further teaches “and a second mixer” (Column 12 lines 8- 15, Column 12 lines 37-39, Column 29 lines 59-62, and Column 1 lines 29-35, The one or more substrates establish a droplet operations surface or gap for conducting droplet operations and may also include electrodes arrange to conduct the droplet operations. The droplet operations substrate or the gap between the substrates may be coated or filled with a filler fluid that is immiscible with the liquid that forms the droplets. Other droplet operations may be effected by varying the patterns of voltage activation; examples include merging, splitting, mixing, and dispensing of droplets. “Droplet operation” means any manipulation of a droplet on a droplet actuator. A droplet operation may, mixing a droplet. The term “mixing” refers to droplet operations which result in more homogenous distribution of one or more components within a droplet.). Therefore the one or more substrates for droplet operations which include mixing teaches to a second mixer. The recitation “ to mix the fluid within the third microfluidic channel while the fluid is at the second temperature.” is capability of the second mixer which is fully capable based on the teachings of the mixer in modified Stephenson.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified Stephenson to incorporate the teachings of Winger wherein there is a second mixer. Doing would allow the device to further mix fluids and magnetic particles to further any reaction that is needed within the device.
Regarding claim 15, Stephenson teaches “A microfluidic magnetic microbead interaction device comprising:” (Para [0014], a device, wherein each droplet of the plurality of droplets comprises a first fluid with a plurality of magnetic particles. The device includes a microchannel); “a body having” Fig. 2, and Para [0095], This partitioning immediately precedes splitting of the droplet at a fork leading to two outlet channels, outlet 1 (branch 817) and outlet 2 (branch 818). Frame 4 (FIG. 8D); “a microfluidic interior” (Para [0002], Microfluidic devices which include one or more microchannels); “and a port connected to the microfluidic interior,” (Para [0085], Immediately after, small copper wire is placed into the still molten electrode ports to provide attachments to electronic power supply. Electrode copper wire connections can be stabilized using an epoxy overlay to minimize breakage of the wire. Other implementations of the electrode configuration exist, including pre-fabricating electrodes on the substrate and aligning the microfluidic channels to these existing electrodes.). The recitation “ the microfluidic interior configured to receive ferromagnetic microbeads having a Curie temperature;” is capability of the microfluidic interior. Stephenson discloses the positively claimed structural elements of the microfluidic interior as claimed, such microfluidic interior are said to be fully capable of the recited adaption in as much as recited and required herein. Further taught “a magnet” (Abstract, A first magnet introduces). The recitation “configured to exert a magnetic force to the microfluidic interior” capability of the magnet. Stephenson discloses the positively claimed structural elements of the magnet as claimed, such magnet is said to be fully capable of the recited adaption in as much as recited and required herein.
Stephenson teaches a heater within (Para [0085), however that is for the production of the device. Therefore Stephenson does not explicitly teach “a heater to heat fluid introduced into the microfluidic interior”.
Winger teaches “a heater” (Column 30 lines 36-42, Column 30 lines 43-61, Heating devices 1025 for controlling the temperature within, for example, certain reaction and/or washing zones of droplet actuator 1005. In one example, heating devices 1025 may be heater bars that are positioned in relation to droplet actuator 1005 for providing thermal control thereof.). The recitation “configured heat fluid introduced into the microfluidic interior” is capability of the heater however taught within (Column 30 lines 43-61 of Winger in that the heating devices control temperature within the reaction, washing and droplet zones.).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Stephenson to incorporate the teachings of Winger a heater to heat fluid introduced into the microfluidic interior. Doing so provides a temperature needed for the process to be conducted on the device. Adding a heater to the device accelerates the reaction process and provides for a device capable of reactions which require temperature regulation.
Further taught by Stephenson “a mixer” (Para [0046], different fluids have likely mixed via diffusion or advection (mechanically driven flow) or convection (thermal driven flow), or some combination.). The recitation “configured to mix the fluid in the microfluidic interior” is capability of the mixer. Stephenson discloses the positively claimed structural elements of the mixer as claimed, such mixers are said to be fully capable of the recited adaption in as much as recited and required herein.
Stephenson also teaches a controller within (Para [0119], other specialized components to aid in performing the inventive functions described herein include one or more field programmable gate arrays (FPGA) (not shown), one or more controllers (not shown), or one or more other special-purpose computer chips.) In addition to “computer-readable instructions stored in a non-transitory computer-readable medium” (Para [0018] and [0107], one or more computer-readable media including one or more sequences of instructions. The computer-readable medium and the one or more sequences of instructions. The computer system 1100 also includes a read only memory (ROM) 1106 or other static storage device coupled to the bus 1110 for storing static information, including instructions.).
Stephenson does not explicitly teach outputting control signals to the heater causing the heater to heat the fluid to the temperature above the Curie temperature of the ferromagnetic microbeads, or outputting control signals to the mixer to mix the fluid and ferromagnetic microbeads while the fluid is at the temperature above the Curie temperature of the ferromagnetic microbeads”.
Winger teaches “and a controller configured to output control signals to the heater causing the heater to heat the fluid” (Column 30 lines 36-42, Column 30 lines 43-61, A controller 1030 of microfluidics system 1000 is electrically coupled to various hardware components of the invention such as heating devices 1025. ). Controller 1030 controls the overall operation of microfluidics system 1000. heating devices 1025 for controlling the temperature within, for example, certain reaction and/or washing zones of droplet actuator 1005. In one example, heating devices 1025 may be heater bars that are positioned in relation to droplet actuator 1005 for providing thermal control thereof.)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Stephenson to incorporate the teachings of Winger wherein the device has a controller configured to output control signals to the heater causing the heater to heat the fluid. Doing so allows the controller to control the setting of the temperature to maintain the needed temperature which is optimal for the process to be conducted on the device. In addition, to increasing the ability to change temperatures fast which is needed for fast thermal cycling.
The recitation “to heat the fluid to the temperature above the Curie temperature of the ferromagnetic microbeads” is capability of the heater. Modified Stephenson discloses the positively claimed structural elements of the heater as claimed, such heater are said to be fully capable of the recited adaption in as much as recited and required herein. In addition, Stephenson teaches Curie as already highlighted above.
Further taught by Winger is “and to output control signals to the mixer to mix the fluid and the ferromagnetic microbeads” (Column 12 lines 8- 15, Column 30 lines 43-61 , Column 13 lines 59-64, A controller 1030 of microfluidics system 1000 is electrically coupled to various hardware components of the invention, such as droplet actuator 1005 any other input and/or output devices (not shown). Controller 1030 controls the overall operation of microfluidics system 1000. “Droplet operation” means any manipulation of a droplet on a droplet actuator. A droplet operation may, for example, include: loading a droplet into the droplet actuator; dispensing one or more droplets from a source droplet; splitting, separating or dividing a droplet into two or more droplets; transporting a droplet from one location to another in any direction; merging or combining two or more droplets into a single droplet; diluting a droplet; mixing a droplet agitating a droplet; deforming a droplet; retaining a droplet in position; incubating a droplet; heating a droplet. “Magnetically responsive” means responsive to a magnetic field. “Magnetically responsive beads” include or are composed of magnetically responsive materials. Examples of magnetically responsive materials include paramagnetic materials, ferromagnetic materials, ferrimagnetic materials, and metamagnetic materials. Examples of suitable paramagnetic materials.)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Stephenson to incorporate the teachings of Winger wherein the and to output control signals to the mixer to mix the fluid and the ferromagnetic microbeads. Doing would allow the controller to control the mixing portion to allow the right amount of fluid to be entered at a given time and to allow the flow rate and amounts to be regulated. This control provides for real-time adjustments to be made for optimal mixing within the device.
Stephenson nor Winger teaches heating while mixing as recited within “while the fluid is at the temperature above the Curie temperature of the ferromagnetic microbeads”.
Selden teaches a biochip having a moving mechanism that includes pneumatic, mechanical, magnetic in addition to “while the fluid is at the temperature above the Curie temperature of the ferromagnetic microbeads” within (Page 4, The treatment first prepares the purified DNA and reaction mixture outside the microfluidic plate, places the plate in the controller, primes the plate, loads and mixes reagents over 45 minutes in the plate, and heats for PCR.)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified Stephenson to incorporate the teachings of Selden wherein the controller is configured to mix and heat at the same time. Doing would increases the reaction time and a more uniform mixed component.
Claim 3 are rejected under 35 U.S.C. 103 as being unpatentable over Stephenson et. al. (WO 2019023159 A1) in view of Winger (US 9513253 B2) and Selden et. al. (KR 20190111165A) as applied to claim 1 above and in further view of Bort et. al. (US 20140161686 A1).
Regarding claim 3, modified Stephenson teaches all of claim 1 as above but does not explicitly teach “wherein the ferromagnetic microbeads are in a lyophilized form prior to introduction of fluid into the microfluidic interior.”.
Bort teaches microfluidic system including a droplet actuator having an interior cavity and a series of electrodes arranged along the interior cavity for forming a droplet-operation path therethrough. In addition to teaching “wherein the ferromagnetic microbeads are in a lyophilized form prior to introduction of fluid into the microfluidic interior” (Para [0091], In one example, bead 1930 is a lyophilized bead. In another example, bead 1930 is an encapsulated liquid reagent. According to aspects of embodiments, one or more encapsulants may be formed of one or more of oil or water. Additional aspects of embodiments include an encapsulant that may be soluble at about room, a temperature above room temperature, and/or a temperature in the range about 25 degrees Celsius to about 100 degrees Celsius.).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Stephenson to incorporate the teachings of Bort wherein the wherein the ferromagnetic microbeads are in a lyophilized form prior to introduction of fluid into the microfluidic interior. Doing so increases the shelf-life of the microbeads which improves their mixing capability.
Claims 5 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Stephenson et. al. (WO 2019023159 A1) in view of Winger (US 9513253 B2) and Selden et. al. (KR 20190111165A) as applied to claim 1 above and in further view of Sharon et. al. (WO 2010114858 A1).
Regarding claim 5, modified Stephenson teaches all of claim 4 as above but does not explicitly teach “wherein the mixer comprises a thermal resistor.”
Sharon teaches an invention relating to the control of fluid flow rate and direction on a microfluidic device which have enriched microbeads could be separated by continuous centrifugation or by filter methods. In addition to teaching “wherein the mixer comprises a thermal resistor.” (Para [0010], [0039], and [0026], a thermal interface which is controlled by a thermal controller for integrated temperature cycling on the microfluidic device. Figure 5 A, a PCR chamber (e.g. PCR channels) or other components are downstream of a high flow chamber (e.g. mixer) in a "low-flow-reservoir-high-flow" microfluidic chip configuration, in which case sample from the mixer can be processed by PCR, using the thermal interface controlled by the thermal controller, as shown in Figure 1.)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Stephenson to incorporate the teachings of Sharon wherein the mixer comprises a thermal resistor. Doing so enables control over reaction kinetics and maintaining required temperatures throughout the mixing process which increases the effectiveness of mixing.
Regarding claim 6, modified Stephenson teaches all of claim 4 as above but does not explicitly teach “comprising a thermal resistor, thermal resistor serving as the heater and the mixer”.
Sharon teaches “comprising a thermal resistor, thermal resistor serving as the heater and the mixer”. (Para [0010], [0039], and [0026], a thermal interface which is controlled by a thermal controller for integrated temperature cycling on the microfluidic device. Figure 5 A, a PCR chamber (e.g. PCR channels) or other components are downstream of a high flow chamber (e.g. mixer) in a "low-flow-reservoir-high-flow" microfluidic chip configuration, in which case sample from the mixer can be processed by PCR, using the thermal interface controlled by the thermal controller, as shown in Figure 1. Where the thermal interface comprises a PCR thermal cycling device with a ceramic heater and air cooling.)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Stephenson to incorporate the teachings of Sharon comprising a thermal resistor, thermal resistor serving as the heater and the mixer. Doing enables control over reaction kinetics and maintaining required temperatures throughout the mixing process which increases the effectiveness of mixing and rapid temperature control for the heater.
Response to Amendments
Claim Amendments
Applicants amendments to claim 10 have overcome the 112b rejections set forth in the non-final office action dated 11/24/2025.
Drawing Amendments
The Drawing objections set forth in the office action of 11/24/2025 is resolved with the exception of the microfluidic channel. Applicant points to the comparison within the specifications to the drawings for all other of the drawing objections set forth in the non-final.
Response to Arguments
Applicant's arguments filed 12/16/2025 have been fully considered.
Examiner has withdrawn the objection to claim 7.
Applicant traverses the 103 rejections set forth in the non-final office action. Examiner has made new 103 rejections based on claim amendments.
Applicant argues that the claim amendments within claim 1 is not disclosed within the current rejection.
Examiner disagrees and the cited art does disclose the claimed features.
Applicant argues Stephenson nor Winger teaches or suggest a controller that is configured to "output control signals to the heater causing the heater to heat the fluid to the temperature above the Curie temperature of the ferromagnetic microbeads and output control signals to the mixer to mix the fluid and ferromagnetic microbeads while the fluid is at the temperature above the Curie temperature of the ferromagnetic microbeads.”
Examiner disagrees and states that the controller configured to output controls is disclosed and the remainder of the claim in which the fluid is at a temperature above the curie temperature is capability of the fluid. Examiner has made a new 103 rejection in which all of the positively claimed features are disclosed.
Applicant argues that the cited references do not establish a prima facie obviousness for independent claim 1 and claim 15 is patentable for the same reasons as claim 1. In addition, claims 2-10 are dependent from claim 1 and patentable for the same reasons as claim 1.
Examiner maintains the obviousness rejections based on the recitations stated in the rejections.
Applicant argues that the application is in condition for allowance.
Examiner has made new 103 rejections based on claim amendments.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/V.E.H./Examiner, Art Unit 1798
/CHARLES CAPOZZI/Supervisory Patent Examiner, Art Unit 1798