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 .
Election/Restrictions
Applicant’s election without traverse of claims 1-5 in the reply filed on 12/19/2025 is acknowledged.
Claims 6-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/19/2025.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 5/9/2023 is being considered by the examiner.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 2 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al. (US 20060140051 A1)(provided by the Applicant’s IDS of 05/29/2023) in view of Liu et al. (US 20030175947 A1)(provided by the Applicant’s IDS of 05/29/2023).
Regarding claim 1, Kim teaches a method comprising:
receiving, at a microfluidic channel (microchannel), a biologic sample including a cell (para. 0030);
providing a magnetic field within the microfluidic channel using a first magnet (one of the electromagnets corresponds to f4 in Fig. 7)(para. 0012, electromagnets operating to provide a magnetic field), wherein the magnetic field attracts a first plurality of magnetic particles (para. 0030, magnetic material that are microbeads, hereinafter magnetic microbeads; destinate half of the magnetic microbeads introduced to the channel as the “first plurality of magnetic particles”) disposed within the microfluidic channel (para. 0031, mixing sample containing magnetic microbeads by operating the two or more electromagnets, the act of mixing by operating electromagnets involves attracting) and agitate a volume of fluid (the volume of fluid that is within the mixing effect causes by the set of electromagnets corresponds to f4 in Fig. 7) within the microfluidic channel (para. 0031, mixing);
in response to agitating the volume of fluid, moving the first plurality of magnetic particles through the microfluidic channel to lyse the cell and to release cellular material from the cell (para. 0039).
Kim teaches a microfluidic device including a microchannel and electromagnets (para. 003). Kim teaches operating the electromagnets in combination with magnetic microbeads for mixing sample and lysing cells (paras. 0003 and 0012). Kim fails to teach activating a first resistor disposed within the microfluidic channel to agitate the volume of fluid within the microfluidic channel.
However, Liu teaches a microfluidic device. Liu teaches the device includes a resistive heater, which when used in combination with injected gas bubbles causes oscillating flow, and thus enhances mixing in the device (abstract, paras. 0029 and 0066 ).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the microfluidic channel taught by Kim to include a resistive heater (resistor) taught by Liu in order to enhance mixing when used with gas bubbles with a reasonable expectation of success (Liu, abstract) (MPEP 2143)(I)(G).
The teachings of Kim as modified with Liu would yield activating a first resistor (resistive heater of Liu) disposed within the microfluidic channel to agitate the volume of fluid within the microfluidic channel (Liu, resistive heater is used to enhance mixing).
Regarding claim 2, modified Kim teaches all of the elements of the current invention as stated above with respect to claim 1. Modified Kim further teaches wherein moving the first plurality of magnetic particles includes moving the first plurality of magnetic particles at a different velocity than a velocity of surrounding fluid (paras. 0003 and 0051-052 and Fig. 7, the device is mixing sample and the magnetic beads and lysing cells in flow configuration; mixing means the magnetic beads are moving in different directions and thus the magnetic beads are all moving at a different velocities as compared to the overall flow which is in the direction of inlet to outlet), thereby generating local shear near the cell (para. 0052, lysing of cell, and thus discloses the motions of the magnetic beads generate a shearing force near the cell and thus disrupt and lyse the cell).
Regarding claim 5, modified Kim teaches all of the elements of the current invention as stated above with respect to claim 1. Kim further teaches
providing a second magnetic field within the microfluidic channel using a second magnet (one of the electromagnets that corresponds to f1 in Fig. 7)
wherein the second magnetic field attracts a second plurality of magnetic particles (the other half of the magnetic beads introduced) disposed within the microfluidic channel (para. 0031); and
wherein the first plurality and second plurality of magnetic particles are to lyse the cell (para. 0039 and 0052), and the first magnet is downstream from the second magnet.
Modified Kim does not teach the location of the first resistor and does not disclose a second resistor and thus fails to teaches activating a second resistor disposed within the microfluidic channel to agitate a second volume of fluid within the microfluidic channel, and in response, moving the second plurality of magnetic particles through the microfluidic channel, and the first magnet and the first resistor are downstream from the second magnet and the second resistor within the microfluidic channel.
However, Kim teaches there are four sets of electromagnets along the length of the microchannel (Kim, Fig. 7) indicating that there are four zones along the length of the microchannel that require fluid motions for mixing (para. 0005 and 0042). In addition, Liu teaches a microfluidic device. Liu teaches the device includes a resistive heater, which when used in combination with injected gas bubbles causes oscillating flow, and thus enhances mixing in the device (abstract, paras. 0029 and 0066).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the microfluidic channel taught by including three additional resistive heaters (resistors) taught by Liu and along with the first resistive heater (from claim 1), and position each resistor in each zone adjacent to the each set of electromagnets where mixing is needed in order to enhance mixing when used with gas bubbles at the appropriate locations along the length of the microchannel (Kim, Fig. 7, paras. 0005 an 0042) with a reasonable expectation of success (Liu, abstract and Kim, Fig. 7, paras. 0005 an 0042) (MPEP 2143)(I)(G).
The teachings of modified Kim would yield activating a second resistor (the resistive heater adjacent to the electromagnets corresponds to f1 in Fig. 7) disposed within the microfluidic channel to agitate a second volume of fluid within the microfluidic channel, and in response, moving the second plurality of magnetic particles (the other half of the magnetic beads introduced) through the microfluidic channel, and the first magnet (one of the electromagnets corresponds to f4 in Fig. 7) and first resistor (the resistive heater adjacent to the electromagnets corresponds to f4 in Fig. 7) are downstream from the second magnet (one of the electromagnets corresponds to f1 in Fig. 7) and the second resistor (locate corresponds to f1 in Fig. 7) within the microfluidic channel.
Claims 1-2 are rejected under 35 U.S.C. 103 as being unpatentable over Hwang et al. (US 20120107823 A1) in view of Sista et al. (US 20150314293 A1) and further in view of Markel et al. (WO 2018009458 A1).
Regarding claim 1, Hwang teaches a method comprising:
receiving, at a microfluidic channel (chamber 22)(Fig. 1), a biologic sample including a cell (para. 0060);
confining a first plurality of magnetic particles (half of the beads 28)(para. 0054, micro-units/beads 28 are magnetic beads) within the microfluidic channel (abstract, Fig. 1 and para. 0054);
activating actuation of vibrating a membrane to agitate a volume of fluid within the microfluidic channel (para. 0064);
in response to agitating the volume of fluid, moving the first plurality of magnetic particles through the microfluidic channel to lyse the cell and to release cellular material from the cell (para. 0064).
Hwang teaches beads 28 (the first plurality of magnetic particles) are physically confined in chamber 22, which has inlet and outlet diameters to be less than the diameter of beads 28 (para. 0060) and thus fails to teach providing a magnetic field within the microfluidic channel using a first magnet, wherein the magnetic field attracts a first plurality of magnetic particles disposed within the microfluidic channel.
However, Sista teaches a microfluidic device comprising magnetic beads and a magnet (electromagnet, paras. 0089, 0097 and 0099). Sista further teaches beads can be confined either by physical structures or by a magnetic field (paras. 0097 and 0099). Sista further teaches the beads can be released by removing the magnetic field by turning off the magnet (paras. 0089 and 0105).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted physically confining the magnetic beads taught by Hwang with confining with a magnetic field through providing a magnet to as taught by Sista because one of ordinary skill in the art would accordingly have recognized the a magnet field with a magnet would result in the predictable result of providing a means for confining the magnetic beads in chamber 22 of Hwang.
The teachings of modified Hwang would yield providing a magnetic field within the microfluidic channel using a first magnet (electromagnet of Sista), wherein the magnetic field attracts a first plurality of magnetic particles disposed within the microfluidic channel (para. 0296). The magnetic field can also be removed to release the beads as necessary (Sista, 0105).
In addition, Hwang teach fluid motions in the chamber 22 is actuated by vibrating membrane 26 (para. 0064), and thus fails teach activating a first resistor disposed within the microfluidic channel to agitate a volume of fluid within the microfluidic channel;
However, Hwang teaches motion can be provide through a membrane or thermo-pneumatic (Hwang, para. 0061). Furthermore Markel teaches a microfluidic device for fluid mixtures. Markel teaches the device comprises fluid actuators for fluid motions. Markel further teaches the fluid actuator may as inertial pumps including, for example, thermal actuators that has a thermal resistor, piezo-membrane based actuators, or any combination thereof (Markel, paras. 0022, 0024).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified chamber 22 taught by Hwang to include a thermal resistor taught by Markel in order to an additional fluid motion actuation means for the device with a reasonable expectation of success (Hwang, para. 0061 and Markel, paras. 0022, 0024) (MPEP 2143)(I)(G).
The teachings of modified Hwang would yield activating a first resistor (thermal resistor of Markel, para. 0024) disposed within the microfluidic channel to agitate the volume of fluid within the microfluidic channel; and in response to agitating the volume of fluid, moving the first plurality of magnetic particles through the microfluidic channel to lyse the cell and to release cellular material from the cell.
Regarding claim 2, modified Hwang teaches all of the elements of the current invention as stated above with respect to claim 1. Modified Hwang further teaches wherein moving the first plurality of magnetic particles (beads 28) includes moving the first plurality of magnetic particles at a different velocity than a velocity of surrounding fluid (para. 0064, oscillating motions of beads that lead to shearing of cell discloses beads 28 are moving in different velocity than the surrounding fluid), thereby generating local shear near the cell (para. 0064).
Claims 4 are rejected under 35 U.S.C. 103 as being unpatentable over Hwang et al. (US 20120107823 A1) in view of Sista et al. (US 20150314293 A1) and further in view of Markel et al. (WO 2018009458 A1) as applied to claim 1 and further in view of Bradley et al. (US 20070132043 A1).
Regarding claim 4, modified Hwang teaches all of the elements of the current invention as stated above with respect to claim 1. Modified further including: applying energy to the first magnet (electromagnet of Sista, para. 0089) to provide the magnetic field (para. 0097, magnetically retaining magnetic beads).
Modified Hwang teaches the magnet beads is confined by the magnetic field generated by an electromagnet of Sista (see above). Hwang teaches when a sample with cell is introduced into the chamber 22, the first resistor (thermal resistor of Markel) and/or vibration of membrane 26 of Hwang is actuated to induce fluid motion such that the motion of beads 28 (the first plurality of magnetic particles) causes shearing and lysing the cells (see above). Hwang does not explicitly teach beads 28 confined by the magnetic field is released for motion prior to the actuation of the first resistor and/or vibration of the membrane and thus modified Hwang fails to teach removing the energy to remove the magnetic field (paras. 0089) and release the first plurality of magnetic particles prior to activating the first resistor.
However, Bradley teaches a microfluidic device comprising magnetic beads and a magnet. Bradley teaches the magnetic beads are held in place by a magnet (para. 0208), and then the magnetic beads are released by removing the magnetic field to allow for the magnetic beads to flow (para. 0209).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Hwang to include removing the energy to remove the magnetic field (paras. 0089) and release the first plurality of magnetic particles prior to activating the first resistor in order to for the magnetic beads to be released for freer motions prior to activating the first resistor (with a reasonable expectation of success (Bradley, para. 0209) (MPEP 2143)(I)(G).
Claims 5 are rejected under 35 U.S.C. 103 as being unpatentable over Hwang et al. (US 20120107823 A1) in view of Sista et al. (US 20150314293 A1) and further in view of Markel et al. (WO 2018009458 A1) as applied to claim 1 and further in view of Kim et al. (US 20060140051 A1)(provided by the Applicant’s IDS of 05/29/2023).
Regarding claim 5, modified Hwang teaches all of the elements of the current invention as stated above with respect to claim 1.
Hwang teaches a micro-device for cell lysis (abstract, para. 0008). Hwang teaches the micro-device comprises chamber 22 (microchannel) that includes magnetic beads (beads 28). Modified Hwang teaches the magnet beads confined by the magnetic field generated by a first magnet (electromagnet). Hwang teaches when a sample with cell is introduced into the chamber 22, the first resistor (thermal resistor of Markel) and/or vibration of membrane 26 of Hwang is actuated to agitating a volume of fluid such that the motions of beads 28 (half of the beads 28 is destinated as the first plurality of magnetic particles) causes shearing and lysing the cells.
Modified Hwang does not teach a second magnet and a second resistor and thus fails to teach
providing a second magnetic field within the microfluidic channel using a second magnet, wherein the second magnetic field attracts a second plurality of magnetic particles disposed within the microfluidic channel; and
activating a second resistor disposed within the microfluidic channel to agitate a second volume of fluid within the microfluidic channel, and in response, moving the second plurality of magnetic particles through the microfluidic channel, wherein the first plurality and second plurality of magnetic particles are to lyse the cell, and the first magnet and the first resistor are downstream from the second magnet and the second resistor within the microfluidic channel.
However, Kim teaches a microfluidic device comprising a microchannel, electromagnets and microbeads for mixing and lysing cells (para. 0003). Kim teaches the electromagnets are actuators for fluid motion that drive the microbeads to lysing cells. Kim teaches the device can comprise more than one sets of electromagnets (Fig. 7), with each set providing sufficient mixing for a zone in the microchannel (para. 0042), to avoid dead volume (para. 0005).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the microfluidic channel taught by modified Hwang to include an additional magnet and resistor (actuator for fluid motion) in a zone upstream of the first magnet and the first resistor to ensure there is sufficient fluid motion in the entire chamber 22 as taught by Kim in order to prevent having a dead volume with a reasonable expectation of success (Kim, Fig. 7 and paras. 0005 and 0042) (MPEP 2143)(I)(G). Furthermore, modified Hwang discloses the claimed invention except for the second magnet and second resistor. It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have duplicate the magnet and resistor, since it have been held that a mere duplication of working parts of a device involves only routine skill in the art. One would have been motived to duplicate the magnet and resistor for the purpose of sufficient mixing and avoiding have a dead volume. “Mere duplication of parts has no patentable significance unless a new and unexpected result is produced” In re Harza, 274 F.2d 669, 124 USPQ 378 (CCPA 1960) See MPEP 2144.04(VI)(B).
The teachings of modified Hwang would yield providing a second magnetic field within the microfluidic channel using a second magnet (an additional magnet), wherein the second magnetic field attracts a second plurality of magnetic particles (the other half of the beads 28) disposed within the microfluidic channel; and
activating a second resistor (an additional thermal resistor of Markel) disposed within the microfluidic channel to agitate a second volume of fluid within the microfluidic channel, and in response, moving the second plurality of magnetic particles through the microfluidic channel, wherein the first plurality and second plurality of magnetic particles are to lyse the cell, and the first magnet and the first resistor are downstream from the second magnet and the second resistor within the microfluidic channel (the additional magnet and thermal resistor are placed upstream of the first set).
Claims 3 are rejected under 35 U.S.C. 103 as being unpatentable over Hwang et al. (US 20120107823 A1) in view of Sista et al. (US 20150314293 A1) and further in view of Markel et al. (WO 2018009458 A1) as applied to claim 1, further in view of Bradley et al. (US 20070132043 A1), and further in view of Nishimura (JP 2006116083 A).
Regarding claim 3, modified Hwang teaches all of the elements of the current invention as stated above with respect to claim 1.
Modified Hwang teaches the magnet beads confined by the magnetic field generated by an electromagnet. Hwang teaches when a sample with cell is introduced into the chamber 22, the first resistor (thermal resistor of Markel) and/or vibration of membrane 26 of Hwang is actuated to agitating a volume of fluid such that the motions of beads 28 (the first plurality of magnetic particles) causes shearing and lysing the cells. Hwang does not explicitly teach the beads 28 confined by the magnetic field is released for motion prior to the actuation of the first resistor and/or vibration of the membrane and thus fails to teach further including heating the first plurality of magnetic particles prior to agitating the volume of fluid to control magnetic properties of the first plurality of magnetic particles.
However, Bradley teaches a microfluidic device comprising magnetic beads and a magnet. Bradley teaches the magnetic beads are held in place by a magnet (para. 0208), and then the magnetic beads are released by removing the magnetic field to allow for the magnetic beads to flow (para. 0209).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Hwang to include removing the energy to remove the magnetic field (paras. 0089) and release the first plurality of magnetic particles prior to agitating the volume of fluid in order to for the magnetic beads to be released for freer motion prior to agitating the volume of fluid with a reasonable expectation of success (Bradley, para. 0209) (MPEP 2143)(I)(G).
Modified Hwang teaches releasing the magnetic particles by removing the energy to remove the magnetic field (see above) and thus still fails teach heating the first plurality of magnetic particles prior to agitating the volume of fluid to control magnetic properties of the first plurality of magnetic particles.
However, Nishimura teaches when the magnetic particles are heated at above the Curie temperature, the magnetic particles are released from the influence of the static magnetic field and are not accumulated and retained at a predetermined position (para. 0037).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted removing the energy to remove the magnetic field taught by modified Hwang with heating the first plurality of magnetic particles because one of ordinary skill in the art would accordingly have recognized the removing the magnetic field or heating the first plurality of magnetic particles would result in the predictable result of providing a means to disrupt the magnetic influence on beads 28 and thus allow for releasing beads 28 to freer motions prior to agitating the volume of fluid.
The teachings of modified Hwang would yield heating the first plurality of magnetic particles prior to agitating the volume of fluid to control magnetic properties of the first plurality of magnetic particles (heating to Curie temperature as taught by Nishimura would alter the magnetic properties of the first plurality of magnetic particles).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MAY CHIU whose telephone number is (571)272-1054. The examiner can normally be reached 9 am - 5 pm.
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/M.L.C./ Examiner, Art Unit 1758
/MARIS R KESSEL/ Supervisory Patent Examiner, Art Unit 1758