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 .
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim Status
Claims 9-16, 18, 20, 27 are still pending.
Claims 1-8, 17, 19 have been canceled.
Claims 9, 12 have been amended.
Clams 22-26 have been withdrawn.
Claim 27 is new.
Claim Objections
Claim 27 is objected to because of the following informalities:
Claim 27 recites “The method of claim 9” should read as “The microfluidic device of claim 9”. Appropriate correction is required.
Claim Rejections - 35 USC § 102
Claim 9-15, 18, and 20 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Ward et. al. (US 20170248508 A1).
Regarding claim 9, Ward teaches “A microfluidic device comprising:” (Abstract, microfluidic devices); “a sorting channel” (Para [0158], The magnetic separator can be any device that can generate a magnetic field such as a magnetic-activated cell sorting (MACS) column) “arranged in a substrate and” (Para [0176], For example, a magnetic separator can comprise a first substrate comprising a channel,).
The recitation “configured to flow a fluid sample comprising magnetized target entities;” is capability of the sorting channel. Ward discloses the positively claimed structural elements of the sorting channel as claimed, such sorting channel are said to be fully capable of the recited adaption in as much as recited and required herein.
Ward further teaches, “a magnet placed underneath the substrate under the sorting channel;” (Para [0159], The strength of the gradient can be controlled by the adjusting the number of magnets, the magnetic force of the magnets, and/or the alignment of the magnets. FIG. 19A illustrates arrangements of magnets relative to a microfluidic channel in a magnetic separator. FIG. 19A illustrates a plurality of magnets arranged above a microfluidic channel (e.g., above a tape or other lid), where the plurality of magnets have alternating polarities, wherein the polarities alternate in a flow direction of the microfluidic channel. Therefore, the sorting channel is on the magnetic separator which has a first substrate and the magnet can be shown underneath the channel which has the substrate.
Ward further teaches, “a permeability channel arranged in the substrate adjacent to and along a first side of the sorting channel and comprising a set of high magnetic permeability particles retained within the permeability channel;” (Paras [0110], [0157], and [0159], [0163], [0070], and Fig 10B, The magnetic region can also be an array of microposts (e.g., made from plastic) embedded with magnetic particles. These microposts can induce local magnetic fields that attract the particles with magnetically susceptible labels and free magnetically susceptible labels as they flow through the array. Once the external magnetic field is removed the microposts may no longer attract the particles with magnetically susceptible labels, which can then be eluted form the device. A “car wash” device can comprise a plurality of inlets and a plurality of outlets with one or more DLD arrays (e.g., with tilted obstacles array) disposed there between. The plurality of inlets can be configured to flow a plurality of flow streams toward the plurality of outlets, wherein the plurality of flow streams each comprises a separate fluid. A third stream can comprise a fix and permeabilization stream. Particles with magnetically susceptible labels can be left in the magnetic separator, or flushed out and collected. A spatially non-uniform permanent magnet or electromagnet can be used to create organized and, in some cases, periodic arrays of magnetic particles within an otherwise untextured microfluidic channel. Any magnet combinations that result in a strong pull force on the magnetically-labeled particles can be used here. The methods can comprise flowing a sample through a deterministic lateral displacement (DLD) array of obstacles in a microfluidic channel.).
Therefore, the DLD array that has the micropost embedded with the magnetic particles which is shown prior to the magnetic chamber is the permeability channel adjacent and along a first side of the sorting channel.
The recitation “and wherein the magnet and the set of high magnetic permeability particles are configured to generate a deflecting magnetic field that causes a subset of magnetized target entities in the sorting channel to be deflected away from a first side of the sorting channel” is capability of the magnet and the set of high magnetic permeability particles.
Ward discloses the positively claimed structural elements of the magnet and the set of magnetic permeability particles, such magnet and the set of high magnetic permeability particles are said to be fully capable of the recited adaption in as much as recited and required herein.
Further taught by Ward “and wherein the fluid sample does not flow through the permeability channel. (Para [0071], Claims 13, 14 and Figs 6A-D, Particles of at least a critical size in the sample are deflected by the DLD array to a bypass channel connected to a product outlet. A method for separating or concentrating particles in a fluid sample comprising passing said fluid sample through the system of claim 1. The method of claim 13, wherein cells or other particles in said fluid sample are labeled with extrinsic magnetically susceptible labels through an antibody recognizing said cells or particles.) Therefore the bypass channel within part of the DLD array only allows the particles within the sample to flow through not the fluid sample itself.
Regarding claim 10, Ward teaches all of claim 9 as above. The recitation “wherein the set of magnetic permeability particles are configured to increase a gradient of the deflecting magnetic field” is capability of the magnetic permeability particles. Ward discloses the positively claimed structural elements of the magnetic permeability particles as claimed, such magnetic permeability particles are said to be fully capable of the recited adaption in as much as recited and required herein.
Regarding claim 11, Ward teaches all of claim 9 as above. The recitation “wherein the set of magnetic permeability particles are configured to change a direction of force exerted by the deflecting magnetic field on the magnetized target entities” is capability of the magnetic permeability particles. Ward discloses the positively claimed structural elements of the magnetic permeability particles as claimed, such magnetic permeability particles are said to be fully capable of the recited adaption in as much as recited and required herein.
Regarding claim 12, Ward teaches all of claim 9 as above. The recitation “wherein: the deflecting magnetic field causes a second subset of magnetized target entities in the sorting channel to be deflected towards a second side of the sorting channel;” is capability of magnetic permeability particles which as claimed are configured to generate the deflecting magnetic field. . Therefore Ward discloses the positively claimed structural elements of the magnetic permeability particles as claimed, such magnetic permeability particles are said to be fully capable of the recited adaption in as much as recited and required herein. Further taught is “and the device further comprises: a second permeability channel adjacent to the second side of the sorting channel opposite to the first side of the sorting channel, wherein the second permeability channel comprises a second set of magnetic permeability particles.” (Para, [0159], The systems can comprise a plurality of channels having magnetic regions, e.g., to increase volumetric throughput. In some cases, these channels may be stacked vertically. The magnetic region can be metallic elements fabricated in or near the channel that create an induced local magnetic field in the presence of an external magnetic field.). Therefore, a second magnetic region (DLD array with micropots with magnetic particles) which is near the channel that creates the magnetic fired teaches to the second permeable channel adjacent to the second side of the sorting channel.
Regarding claim 13, Ward teaches all of claim 12 as above in addition to “further comprising: a first collection channel extending from the first side of the sorting channel such that the subset of magnetized target entities flows from the sorting channel to the first collection channel; (Para [0017] and Fig. 10D, concentrator with the DLD array, wherein the concentrator is a microfluidic channel comprising an inlet, a second array of obstacles, a product outlet, and a waste outlet); “and a second collection channel extending from the second side of the sorting channel such that the second subset of magnetized target entities flow from the sorting channel to the second collection channel.” (Para [0146], For example, a concentrating device can be a 2-stage concentrator, in which the first stage comprises a DLD array and the second stage comprises a DLD array. For a multiple-stage concentrating device, each stage can concentrate a sample for the same or different folds.).
Regarding claim 14, Ward teaches all of claim 13 as above in addition to “further comprising: a magnetic permeability strip placed underneath the sorting channel in the substrate adjacent to the magnet, wherein the magnetic permeability strip extends longitudinally along a direction of fluid flow in the sorting channel,” (Paras [0159], [0163], and Fig. 10 C, The magnetic separator herein can comprise a source of a magnetic field. In some cases, the source of the magnetic field can include hard magnets, soft magnets, electromagnets, superconductor magnets, or a combination thereof. Accumulation of magnetic particles can occur on a lid (e.g., tape-side) surface. A magnet can cover the full-width of a microfluidic channel, and an alternating stack can cover the full length of the microfluidic channel.). The recitation “and the magnetic permeability strip is configured to intensify the gradient of the deflecting magnetic field” is capability of the magnetic permeability strip. Ward discloses the positively claimed structural elements of the magnetic permeability strip as claimed. As such, magnetic permeability strip are fully capable of the recited adaption in as much as recited and required herein.
Regarding claim 15, Ward teaches all of claim 9 as above in addition to “further comprising a second sorting channel in the substrate.” (Para, [0073], [0083], [0171], and [0177], For example, methods, devices, and systems herein can comprise DLD arrays and magnetic separators. [0083] In another aspect, the systems herein can further comprise other components for particle separation, detection and/or analysis. In some cases, a system can comprise one or more particle separators other than DLD arrays or magnetic separators. For example, a system can comprise a fluorescence-based particle separator, such as a flow cytometer (e.g., a fluorescence-activated cell sorter). In some cases, a sample can be passed through multiple magnetic fields (e.g., in the same magnetic separator or multiple magnetic separators). The multiple magnetic fields can have different magnetic field gradients. In some cases, a sample can be passed through multiple magnetic field gradients, e.g., a series of magnetic field gradients with increased or decreased magnetic field strengths.). The recitation “and configured to receive a portion of the sample fluid flowing from the sorting channel.” Is capability of the second sorting channel. Ward discloses the positively claimed structural elements of the second sorting channel as claimed, and such second sorting channel is fully capable of the recited adaption in as much as recited and required herein.
Regarding claim 18, Ward teaches all of claim 9 as above in addition to “wherein: the permeability channel includes an array of pillar structures sized to stabilize the set of magnetic permeability particles within the permeability channel.” (Para, [0157] and [0440], The magnetic region can also be an array of microposts (e.g., made from plastic) embedded with magnetic particles. These microposts can induce local magnetic fields that attract the particles with magnetically susceptible labels and free magnetically susceptible labels as they flow through the array. The first microchip contains an array of microposts arranged to specifically separate cells larger than ˜6.0 μm).
Regarding claim 20, Ward teaches all of claim 9 as above in addition to “further comprising: a second magnet placed above the substrate; and wherein North poles of each of the magnet and the second magnet are facing an upward direction.” ( Para [0151] and Fig. 19A, the two magnet stacks. The North poles of alternating magnetic strips within the first within the first magnetic stack is facing upward along with the corresponding alternating magnetic strip within the second magnetic stack. In some cases, these channels may be stacked vertically. In some cases, a magnetic separator can comprise a stack of magnets. For example, the magnets can be arranged with poles alternating and/or stacked side by side).
Regarding claim 27, Ward teaches the deice of claim 9, in addition to “wherein the set of high magnetic permeability particles is retained within the permeability channel by a set of pillars arranged near an end of the permeability channel.” (Paras [0110], [0157], and [0159], and Fig 10B, The magnetic region can also be an array of microposts (e.g., made from plastic) embedded with magnetic particles. These microposts can induce local magnetic fields that attract the particles with magnetically susceptible labels and free magnetically susceptible labels as they flow through the array. Once the external magnetic field is removed the microposts may no longer attract the particles with magnetically susceptible labels, which can then be eluted form the device. A “car wash” device can comprise a plurality of inlets and a plurality of outlets with one or more DLD arrays (e.g., with tilted obstacles array) disposed there between. The plurality of inlets can be configured to flow a plurality of flow streams toward the plurality of outlets, wherein the plurality of flow streams each comprises a separate fluid. A third stream can comprise a fix and permeabilization stream. Particles with magnetically susceptible labels can be left in the magnetic separator, or flushed out and collected. A spatially non-uniform permanent magnet or electromagnet can be used to create organized and, in some cases, periodic arrays of magnetic particles within an otherwise untextured microfluidic channel.). Therefore, the micropost are the pillars that retain the magnetic particles near the end of the DLD as they are retained throughout the DLD which is the permeability channel.
Claim Rejections - 35 USC § 103
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Ward et. al. (US 20170248508 A1) and further in view of Kapur (US 9610582).
Regarding claim 16, Ward teaches all of claim 9 as above but does not teach “further comprising: an inertial focusing channel in the substrate and comprising a set of asymmetric serpentine segments”.
Kapur teaches “further comprising: an inertial focusing channel in the substrate” (Para, [16], within the second microfluidic channel, and such that the particles within the second fluid sample are focused to one or more streamlines within an inertial focusing section of the particle concentration module. [25], By focusing the particles along defined streamlines, the particles can be positioned at precise locations prior to entering the concentrator region, which enables, in certain implementations, the concentrator to more effectively enrich the particle concentration within the buffer sample.); “and comprising a set of asymmetric serpentine segments,” (Para (47) Pre-focusing can be achieved using inertial focusing, where the structure and arrangement of the fluid pathways are designed to generate forces that drive particles within a fluid sample to desired streamlines. The particle focusing section shown in FIG. 5 includes a dividing wall 502 that separates two microfluidic channels 504 fluidly coupled to the output of the filter arrays. Each channel 504 has an undulating pathway defined by the surfaces of the dividing wall 502 and the outer channel walls, where the contour of the dividing wall surfaces match the contour of the outer channel wall it is facing. With the undulating pathways shown in FIG. 5, the microfluidic channels alternate between regions having relatively high curvature and regions having relatively low curvature.).
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 Ward to incorporate the teachings of Kapur wherein an inertial focusing channel in the substrate and comprising a set of asymmetric serpentine segments. Doing creates a device that does not need external forces to align particles for further processing and manipulation. Have the channel be asymmetric serpentine segments allows for more surface contact for the particles passing through the channel.
Further Ward does not explicitly teach “wherein the inertial focusing channel is connected to the sorting channel such that a portion of the sample fluid flows from the inertial focusing channel to the first side of the first sorting channel.” However, it would have been clearly within the ordinary skills of an artisan before the effective filing date of the claimed invention to have modified the invention of Ward by having the inertial focusing channel connected to the sorting channel to allow the sample to continue to flow. This is because Kapur teaches that the buffer passes the focusing channel and the particle concentration module contains the filter region, a focusing region, and a concentrator region within (Para [56]). In addition to Kapur’s teachings Ward teaches that the concentrator is connected to the magnetic separator and the concentrator has a channel comprising an inlet, a second array of obstacles, a product outlet, and a waste outlet within (Para [17]). Kapur teaches that he focusing channel is connected the concentrator module and Ward teaches that the concentrator is connected to the magnetic separator which the sorting channel is part of the magnetic separator. Therefore it would have been an obvious engineering choice, to better place the focusing channel in fluid communication with the sorting channel.
Response to Amendments
Claim Amendments
Applicant states claim 1 has been amended to further explain the permeability channel however Examiner believes applicant is referring to claim 9 amendments. Further applicant has added claim 27 which is dependent on claim 9. Examiner highlights that claim 27 is to a method of claim 9 however claim 9 is a device not a method.
Examiner has canceled claims 1-3 and 5-7 therefore the prior 101 double patent rejection has been withdrawn.
Based on claim amendments Examiner has added more teachings of prior arts already disclosed. I
Response to Arguments
Applicant's arguments filed 2/27/2026 have been fully considered.
Applicant argues that the recited prior art Ward does not disclosed the previously claimed permeability channel in addition to the amended permeability channel of claim 9. Examiner acknowledges applicant stated as amended in claim 1 however claim 1 is canceled and Examiner is interpreting as amended claim 9. Applicant argues that within Ward the DLD array and magnetic separator are not arranged adjacent to and along a first side of the sorting channel as presently claimed. Examiner highlights that Ward’s Fig. 10B discloses the DLD array which teaches to the permeability channel which is adjacent and along a first side of the sorting channel which is the microfluidic channel within Fig. 10B.
Applicant argues that Ward fails to teach the DLD array is "arranged in the substrate adjacent to and along a first side of the sorting channel and comprising a set of high magnetic permeability particles retained within the permeability channel and argues that the DLD array is formed from an array of posts. Examiner points to Fig. 10B in that the DLD array adjacent to and along a first side of the sorting channel which is displayed by the microfluidic channel. Using broadest reasonable interpretation of the first side of the sorting channel is side of the sorting channel. Having the flow from the DLD to the microfluidic channel teaches that they are alongside each other. Paras [0176] and [0070] within Ward, teaches the DLD is arranged in the substrate. The DLD is the permeability channel that is another part of the taught microfluidic channel within Ward that is taught to be on the substrate.
Applicant argues that the interpretation of Ward that the posts are embedded with magnetic particles is incorrect. Applicant instead argues that Ward magnetic separator, e.g., a magnetic region, can be made of "microposts (e.g., made from plastic) embedded with magnetic particles" (paragraph 0157). Examiner maintains that Para [0157] of Ward does teach posts embedded with magnetic particles as recited above. Applicant stated this magnetic separator is different from DLD array. Examiner maintains the rejection however is confused to what part of the claim the Applicant is arguing is not taught by Ward.
Applicant argues that Ward also indicates that the system includes both a DLD array and a separate magnetic chamber (see, e.g., FIG. 10C), and does not suggest combining these two elements into one element. Examiner disagrees and maintains the rejection and highlights the present invention claims “a magnet placed under the substrate under the sorting channel and the permeability channel in the substrate adjacent and along a first side of the sorting channel”. Ward teaches this within claim 9 in particular Para [0176] and Fig. 19A show that the magnetic separator comprises a substrate a the comprises a channel and magnets arranged relative to the microfluidic channel in a magnetic separator.
Applicant argues that neither the DLD array, nor the magnetic separator, includes a permeability channel that retains the high magnetic permeability particles along side a sorting channel. Examiner highlights that “a permeability channel that retains the high magnetic permeability particles along side a sorting channel” is not claim language. Rather the present invention claim language is that the permeability channel is along a first side of the sorting channel and the permeability channel has the high magnetic permeability particles. This is taught within (Paras [0110], [0157], and [0159], [0163], [0070], and Fig 10B) within the rejection. Examiner maintains the rejection.
Applicant argues that Ward fails to teach the sorting channel is configured to flow the fluid sample having the magnetized target and the permeability channel which does not have fluid sample flow through it. However, the flow of the fluid is capability of the device and all of the positively claimed features are taught within Ward. Further Ward teaches a bypass channel within the DLD array which has particles from the sample but not the fluid sample itself.
Applicant argues that Ward or in combination of Kapur teaches the device as recited in amended claim 9. Examiner maintains the rejection and has added recitations from Ward to each the positively claimed features that were added in the amendment.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to VELVET E HERON whose telephone number is 571-272-1557. The examiner can normally be reached M-F 8:30am – 4:30 pm.
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/V.E.H./Examiner, Art Unit 1798
/CHARLES CAPOZZI/Supervisory Patent Examiner, Art Unit 1798
Prosecution Insights