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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 10/22/2025 has been entered.
Election/Restrictions
Newly submitted claims 28-29 are directed to an invention that is independent or distinct from the invention originally claimed for the following reasons:
The groups of inventions (Group I, claims 15-20 and 22-23; Group II, claims 28-29) do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features for the following reasons:
Groups I and II lack unity of invention because even though the inventions of these groups require the technical feature of a kit for forming a microfluidic device comprising: a microfluidic chip with at least one wall of a microfluidic chamber, the wall supporting at least one row of at least 3 pillars, where the pillars of the row: are arrayed to form a polyline; have mean diameters of 1-1000 um; have mean separations of 0.2-500 um; have aspect ratios greater than 2:1; and are composed of a material coated with a soft magnetic material; a generator adapted to apply a magnetic field of at least 110 kAmp/m across the at least one row; a fluid suspending superparamagnetic nanoparticles (NPs), the fluid being injectable into the microfluidic chamber via a microfluidic channel, wherein the NPs are self-repellant to reduce agglomeration; and a support comprising a holder for the microfluidic chip in at least one prescribed position and orientation, and a registration feature for registering the generator in a position in which a field line of the magnetic field is at least 75% aligned with the polyline, where the kit, assembled with the generator registered with the chip by the support, while the NPs are in a liquid carrier within the microfluidic chamber, enable the applied magnetic field to substantially distribute the NPs between the pillars, this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Malic et al. (L. MALIC, X. F. ZHANG, D. BRASSARD, L. CLIME, J. DAOUD, C. LUEBBERT, V. BARRERE, A. BOUTIN, S. BIDAWID, J. FARBER, N. CORNEAU and T. VERES, Polymer-based microfluidic chip for rapid and efficient immunomagnetic capture and release of listeria monocytogenes, Lab on a Chip, 2015, 15, 3994-4007; cited in the IDS filed 11/09/2021) in view of Ward et al. (US 20170248508 A1; cited in the IDS filed 11/09/2021). As discussed in the rejection of claim 15 under 35 U.S.C. 103 below, Malic in view of Ward teaches the shared technical features and therefore the groups lack unity of invention.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 28-29 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Response to Amendment
The Amendment filed 09/24/2025 has been entered. Claims 1-7, 9-20, 22-23, and 28-29 remain pending in the application. Claims 1-7, 9-14, and 28-29 are withdrawn.
Applicant’s amendments to the claims have overcome each and every objection previously set forth in the Final Office Action mailed 07/25/2025.
Claim Interpretation
Regarding claim 15, the limitations of “where the generator's magnetic field strength, NPs, pillars, and thickness of the soft magnetic coating, ensure the kit assembled with the generator registered with the chip by the support, while the NPs are in a liquid carrier within the microfluidic chamber, enable the applied magnetic field to substantially distribute the NPs between the pillars in that at least one of the following obtains…” are interpreted as an intended use of the claimed microfluidic device and are not accorded any patentable weight, since the limitations are focused on the use of the generator (e.g. applied magnetic field) with the microfluidic chip and NPs. If applicant desires to specifically claim processes or methods relating to the generator being actuated to distribute NPs as claimed, it is suggested to incorporate computer-functional limitations (see MPEP 2114 (IV)) to the claim, i.e. recite a computer programmed to actuate the generator and NP density as desired. If applicant desires to claim the specific distribution of the NPs, it is suggested to positively recite the microfluidic device comprising NPs in a liquid carrier within the microfluidic chamber, wherein the NPs are substantially distributed between the pillars according to at least one of the conditions (e.g. “a NP density at every point…”) as claimed.
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.
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 15, 17, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Malic et al. (L. MALIC, X. F. ZHANG, D. BRASSARD, L. CLIME, J. DAOUD, C. LUEBBERT, V. BARRERE, A. BOUTIN, S. BIDAWID, J. FARBER, N. CORNEAU and T. VERES, Polymer-based microfluidic chip for rapid and efficient immunomagnetic capture and release of listeria monocytogenes, Lab on a Chip, 2015, 15, 3994-4007; cited in the IDS filed 11/09/2021) in view of Ward et al. (US 20170248508 A1; cited in the IDS filed 11/09/2021).
Regarding claim 15, Malic teaches a kit for forming a microfluidic device (Figs. 1, 3, 4 shows elements for forming a microfluidic device, such as the magnetic capture microfluidic device of Fig. 1), the kit comprising:
a microfluidic chip (Fig. 1, magnetic capture microfluidic device) with a microfluidic chamber (Figs. 1d, 1e, 1g, 1f shows the bottom substrate of a microfluidic chamber, wherein the microfluidic chamber is interpreted as the “capture chamber” shown in Fig. 1) having at least one wall supporting at least one row of at least 3 pillars (Figs. 1d, 1e, 1g, 1f shows a bottom substrate of the central capture chamber, i.e. a wall, supporting a plurality of rows of at least 3 micropillars), where the pillars of each of the at least the row:
are arrayed to form a polyline (Fig. 1d, 1e, 1f shows micropillars that form an arbitrary polyline, i.e. at least 3 micropillars form a polyline);
have mean diameters of 1-1000 um (page 3995, section 2.1, teaches the micropillars have a diameter of 16 um);
have mean separations of 0.2-500 um (Fig. 1d shows the micropillars have a mean separation of about 50 um; page 3996, left column, first paragraph, teaches each column has a pitch of 50 um and shifted relative to the next column by 4.4 um);
have aspect ratios greater than 2:1 (page 3995, section 2.1, teaches the aspect ratio of cylindrical micropillars are 3:1); and
are composed of a non-magnetic material (Fig. 1f and page 3995, section 2.1 teach the micropillars comprise a hard thermoplastic bottom substrate, which is interpreted as a non-magnetic material; section 2.2 teaches a thermoplastic elastomer is used, i.e. non-magnetic material) with a soft magnetic material coating (Fig. 1f and section 2.2 teach micropillars are coated with nickel, i.e. soft magnetic material; page 3995, section 2.1 teaches micropillars are coated with soft magnetic material, nickel);
a generator (page 3996, right column interpreted as “permanent magnets”; note that the instant specification, paragraph [0088], discusses that permanent magnets and other magnetic field generators can be used to generate a magnetic field, thus the BRI of generator includes permanent magnets) adapted to apply a magnetic field across the at least one row (page 3996, right column, teaches magnets are adapted to apply a magnetic field of about 100 kA m^-1, i.e. 100 kAmp/m, which is capable of applying a magnetic field across the at least one row as shown in Figs. 1g, 3, and 4);
a fluid suspending superparamagnetic nanoparticles (NPs) (section 2.3 teaches superparamagnetic nanoparticles were used in suspension), the fluid being injectable into the microfluidic chamber via a microfluidic channel (Fig. 1 shows the microfluidic device having an inlet, i.e. a microfluidic channel; Fig. 4 shows flow of nanoparticles into the microfluidic device, thus the fluid is capable of being injected into a microfluidic chamber via a microfluidic channel at a later time), wherein the NPs are self-repellant to reduce agglomeration (section 2.3 teaches nanoparticles are coated with a layer of hydroxyl-terminated silica shells to reduce magnetic inter-particle interactions, i.e. to reduce agglomeration; thus, the nanoparticles are capable of being self-repellant to reduce agglomeration at a later time due to the silica shell); and
a support (Fig. 1h, M-chip manifold) for holding the microfluidic chip (Fig. 1h, teaches M-chip manifold comprises a microfluidic device holder, which is capable of holding the microfluidic chip as shown in Fig. 1h) in at least one prescribed position and orientation (Fig. 1h shows the M-chip manifold capable of holding the microchip in at least a position and orientation), in registration with the generator (Fig. 1h teaches the M-chip manifold comprising a top holder, i.e. registration feature, for two permanent magnets and the top holder is capable of holding the magnets in registration with the generator; thus, the microfluidic device holder is capable of holding the microfluidic chip in registration with the magnets) wherein a field line of the magnetic field is at least 75% aligned with the polyline (Fig. 1g and 4 shows a magnetic field is at least 75% aligned with a polyline of micropillars; Fig. 3b shows a magnetic field line between micropillars are aligned).
where the generator's magnetic field strength, NPs, pillars, and thickness of the soft magnetic coating, ensure that the kit assembled with the generator registered with the chip by the support, while the NPs are in a liquid carrier within the microfluidic chamber, enable the applied magnetic field to substantially distribute the NPs between the pillars in that at least one of the following obtains (the limitations are interpreted as an intended use of the claimed generator and pillars and are not accorded any patentable weight; however, for purposes of compact prosecution, Malic, section 2.4.1, teaches the generator, i.e. magnets, create an induction of 1.35T and thus have a magnetic field strength; section 2.1 teaches micropillars are coated with a 2 um thick soft magnetic material, thus the pillars and thickness of the magnetic coatings are selected; section 2.3 teaches superparamagnetic nanoparticles were used in suspension; Fig. 4 shows nanoparticles substantially distributed between the pillars):
a NP density at every point between two adjacent pillars of a single row is at least 50% higher than the NP density midway between two adjacent rows (Fig. 4, center pictures, shows the magnetic field strength, NPs, pillars with magnetic coatings structurally capable of allowing every point between two adjacent pillars of a row to have at least 50% higher NP density than the NP density between two adjacent rows, i.e. the row above or below, at a later time; e.g. depending on a magnetic field, amount of NPs, size of the NPs, and/or length of time, the NPs are capable of being distributed as claimed);
a NP density at every point between two adjacent pillars of a single row is at least 50% higher than the NP density a distance normal to the polyline equal to a mean separation of the pillars (interpreted as not required due to the “at least one” statement above);
a mean NP density in inter-pillar spaces between adjacent pillars is at least 10 times higher than a mean NP density within the chamber (interpreted as not required due to the “at least one” statement above);
a magnified view from a direction in which end faces of the pillars are in view, there are no visible gaps in the NP density between adjacent pillars of any single row of the at least one row, and visible gaps across at least 80% of the chamber away from the at least one row (interpreted as not required due to the “at least one” statement above).
While Malic teaches a zoomed in view of magnetic fields between two magnetized pillars being about 100 kAmp/m (Fig. 3b shows magnetic fields between pillars of about 1x10^5 A/m or 100 kAmp/m; section 2.4.1 teaches a magnetic field at the center of the magnetic plate system of about 100 kA/m), and that permanent magnets create an induction of 1.35T, i.e. converted to about 1074 kAmp/m (section 2.4.1), Malic fails to teach explicitly teach the generator adapted to apply a magnetic field of at least 110 kAmp/m across the at least one row.
Ward teaches a microfluidic device for separation and concentration of particles in a sample (abstract; paragraph [0005]). Ward teaches magnets are arranged adjacent to a microfluidic channel (paragraph [0005]). Ward teaches particles comprise magnetically susceptible labels that can be attached to a magnetic region in a magnetic separator (paragraph [0157]). Ward teaches the magnetic region can include an array of microposts embedded with magnetic particles, where these microposts can induce local magnetic fields that attract the particles with magnetically susceptible labels; wherein 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 (paragraph [0157]). Ward teaches the magnetic separator can comprise a magnetic region for generating a magnetic field, and can be fabricated with soft magnetic materials (paragraph [0166]). Ward teaches the magnetic field strength can be between 0.01 and 10 Tesla (paragraph [0167], converted to about 7.96-7957.75 kA/m). Ward teaches an embodiment where the system is capable of generating a magnetic field strength of at least 0.5 Tesla (paragraphs [0006], [0010], [0167]; converted to about 397. 89 kA/m). Ward teaches the magnetic field can be adjusted to influence supra and paramagnetic particles with magnetic mass susceptibility (paragraph [0168]). Ward teaches magnets to create locally high magnetic field gradients to assist in capturing flowing magnetic particles (paragraph [0165]).
Since Ward teaches a microfluidic device with pillars to attract particles, similar to Malic, 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 the generator of Malic to incorporate the teachings of adjusting magnetic field with various magnetic field strength, such as 0.5 Tesla (about 398 kA/m) of Ward (paragraphs [0157],[0167],[0168]) to provide the generator adapted to apply a magnetic field of at least 110 kAmp/m across the at least one row. Doing so would have a reasonable expectation of successfully improving adjustability of the generator to produce a higher magnetic field strength and improve control superparamagnetic nanoparticles with the pillars as discussed by Ward (paragraphs [0165],[0168]).
Furthermore, since Malic teaches the generator capable of applying magnetic fields of about 100 kA/m (Fig. 3b shows magnetic fields between pillars of about 1x10^5 A/m or 100 kAmp/m; section 2.4.1 teaches a magnetic field at the center of the magnetic plate system of about 100 kA/m), which is merely close to the claimed range of 110 kAmp/m, and Ward teaches ranges of magnetic fields of: 0.01 and 10 Tesla (paragraph [0167], converted to about 7.96-7957.75 kA/m), at least .1 Tesla (paragraph [0167]; 159.15 kAmp/m), and 0.5 Tesla (paragraphs [0006], [0010], [0167]; 397.89 kAmp/m), which are in the claimed range of at least 110 kAmp/m, it would have been obvious to have modified Malic to provide the generator adapted to apply a magnetic field of at least 110 kAmp/m across the at least one row (see MPEP 2144.05(I)). I.e., It would have been prima facia obvious to select the claimed range that is merely close to that of Malic and it would have been prima facia obvious to have selected known magnetic fields that are within the claimed range (see MPEP 2144.05(I)). Additionally, it would have been prima facia obvious to have selected the overlapping portion of the range (i.e. at least 110 kAmp/m; at least 159.15 kAmp/m; at least 397.89 kAmp/m) from the taught range of 7.96-7957.75 kA/m, at least 159.15 kAmp/m, or 397.89 kAmp/m (Ward; paragraphs [0006], [0010], [0167]) (In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); see MPEP 2144.05 (I)).
Note that the limitations of “where the generator's magnetic field strength, NPs, pillars, and thickness of the soft magnetic coating, ensure the kit assembled with the generator registered with the chip by the support, while the NPs are in a liquid carrier within the microfluidic chamber, enable the applied magnetic field to substantially distribute the NPs between the pillars in that at least one of the following obtains…” are interpreted as an intended use of the claimed microfluidic device and are not accorded any patentable weight. If applicant desires to specifically claim processes or methods relating to the generator being actuated to distribute NPs as claimed, it is suggested to incorporate computer-functional limitations (see MPEP 2114 (IV)) to the claim, i.e. recite a computer programmed to actuate the generator and NP density as desired.
Note that the apparatus of modified Malic is identical to the presently claimed structure as discussed above. Since modified Malic discloses the claimed “microfluidic chip”, “generator”, and “support” as claimed and therefore, would have the ability to perform the intended uses and functional limitations in the claim. See MPEP 2112.01 (I). Moreover, modified Malic arrangement of the claimed pillars, the generator adapted to apply a magnetic field strength of at least 110 kAmp/m, and support is structurally capable of performing the claimed limitations of “where the generator's magnetic field strength, NPs, pillars, and thickness of the soft magnetic coating, ensure the kit assembled with the generator registered with the chip by the support, while the NPs are in a liquid carrier within the microfluidic chamber, enable the applied magnetic field to substantially distribute the NPs between the pillars in that at least one of the following obtains…”. For example, Malic, Fig. 4, center pictures, shows the magnetic field strength, NPs, pillars with magnetic coatings structurally capable of allowing every point between two adjacent pillars of a row to have at least 50% higher NP density than the NP density between two adjacent rows, i.e. the row above or below, at a later time; i.e. depending on the amount of NPs, size of the NPs, and/or length of time, the NPs are capable of being distributed as claimed. If applicant desires to claim the specific distribution of the NPs, it is suggested to positively recite the microfluidic device comprising NPs in a liquid carrier within the microfluidic chamber, wherein the NPs are substantially distributed between the pillars according to at least one of the conditions (e.g. “a NP density at every point…”) as claimed.
Regarding claim 17, while Malic teaches the hard thermoplastic bottom substrate of the M-chip contains the capture chamber (Fig. 1, page 3995, section 2.1) and a 3D magnetic trap is integrated into a polymeric microfluidic chip (page 3995, right column, first full paragraph), modified Malic fails to explicitly teach: wherein each of the at least one wall of the microfluidic chamber, is provided as an insert into an opening within the microfluidic chip.
Ward teaches a flow channel can be constructed using one or more pieces having obstacles disposed within it (paragraph [0124]). Ward teaches the obstacles can be fabricated on one or more pieces that are assembled to form the flow channel, or they can be fabricated in the form of an insert that can sandwiched between two or more pieces that define the boundaries of the flow channel (paragraph [0124]), wherein materials and methods for fabricating such devices are known in the art (paragraph [0124]). Ward teaches a magnetic separator comprises obstacles, such as an array with obstacles that are magnetic, such that obstacles can attract magnetically labeled particles flowing in a microfluidic channel (paragraph [0162]).
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 the microfluidic chip and microfluidic chamber of modified Malic to incorporate the teachings of obstacles that can attract magnetically labeled particles, where the obstacles can be fabricated as an insert to be sandwiched between pieces of a flow channel of Ward (paragraphs [0124],[0162]) to provide wherein each of the at least one wall of the microfluidic chamber, is provided as an insert into an opening within the microfluidic chip. Doing so would have a reasonable expectation of successfully fabricating the microfluidic chamber with pillars within the microfluidic chip to properly interact with desired particles as taught by Ward (paragraphs [0124],[0162]).
Furthermore, the claimed limitations are obvious because all of the claimed elements were known in the prior art and one skilled in the art could have combined the elements (i.e. the claimed microfluidic chamber with walls provided as an insert into an opening of a channel) by known methods with no change in their respective functions (i.e. allowing for fabrication of a microfluidic device with a chamber within a chip and allowing for sample flow through the chamber), and the combinations yielded nothing more than predictable results (i.e. providing each of the at least one wall of the microfluidic chamber as an insert into an opening within the microfluidic chip would yield nothing more than the obvious and predictable result of enabling fabrication of the microfluidic chip and enabling sample flow through the chamber and chip). See MPEP 2143(A).
Regarding claim 20, Malic further teaches wherein the at least one row of at least 3 micropillars comprises an array of at least 3 rows, each row having at least 3 pillars arranged with a minimum inter-pillar separation of 0.2-500 um (Fig. 1d and e shows at least 3 rows of an array of pillars, each row having at least three micropillars; Figs. 1d and 1e teach separation between neighboring pillars of each row and column is about 50 um; annotated Fig. 3a below teaches the annotated lines, include a row of at least 3 micropillars), the array having at least 2 axes along which the pillars are aligned (as shown in annotated Fig. 3a below, the plane comprises at least 2 axis that include a row of at least 3 aligned micropillars), and the support comprises a plurality of registration features (Fig. 1h teaches the M-chip manifold comprising a top holder, i.e. registration features, for two permanent magnets, wherein the M-chip is shown to have a slot on the left and a slot on the right of the M-chip manifold, i.e. a plurality of registration features) for registering the generator in respective positions (Fig. 1h teaches two slots for holding two permanent magnets, i.e. the generator, in respective positions) in which field lines of the magnetic field are at least 75% aligned with the axes (Fig. 1g and 4 shows a magnetic field is at least 75% aligned with an axis of three micropillars in a row; annotated Fig. 3a below teaches magnetic fields at least 75% aligned with the annotated axes; Fig. 1d, 1e, and 1g and annotated Fig. 3a below show an array of the magnetically coated micropillars; Fig. 3a below, the plane comprises at least 2 axis that include a row of at least 3 micropillars).
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Zoomed and annotated Fig. 3a of Malic: Two annotated lines on the plane resemble two axes on the plane, wherein the lower line is aligned with the X-axis shown and the upper line is angled away from the X-axis, wherein the magnetic field, shown as field lines around the magnetic array, are at least 75% aligned with the two annotated lines.
Claims 16 and 22-23 are rejected under 35 U.S.C. 103 as being unpatentable over Malic in view of Ward as applied to claim 15 above, and further in view of Lin et al. (US 20170283859 A1).
Regarding claim 16, Malic further teaches the kit according to claim 15 further comprising a sample introduction chamber (see below annotated Fig. 1b, interpreted as the left chamber portion where sample is capable of being introduced) and a sample flush reservoir (see below annotated Fig. 1b, interpreted as the right reservoir portion where sample is capable of being flushed out of), the sample introduction chamber coupled to an ingress of the microfluidic chamber by an inlet channel (Fig. 1b shows inlet channels coupled to openings at the central capture chamber, wherein “ingress” is interpreted as structural openings or channels that couple the inlet channel network to the central capture chamber), and the microfluidic chamber coupled to the sample flush reservoir by an outlet channel (Fig. 1b shows an outlet network of channels that couple the central capture chamber to the reservoir at the right end of Fig. 1b).
While Malic teaches capture and release of target bacteria (abstract) and superparamagnetic nanoparticles (section 2.3, first paragraph), modified Malic fails to teach the microfluidic device further comprising an analyte detection chamber, and the microfluidic chamber coupled to the analyte detection chamber by a superparamagnetic nanoparticle (NP) channel.
Lin teaches a microfluidic device capable of cell-trapping and bead-based gene analysis, wherein the device is capable of independent or parallelized, simultaneous assays of cells (abstract). Lin teaches a microfluidic chamber for trapping magnetic microbeads (paragraph [0106], Fig. 5, cell trap 607), wherein the microfluidic chamber (607) is coupled to a detection chamber (reaction chamber 604) by a channel (the channel between elements 607 and 604). Lin teaches the microfluidic chamber is coupled to various inlets and outlets (elements 609, 611, and 610). Lin teaches purging the device of excess cells once a cell is trapped (paragraph [0009]).
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 the microfluidic device of Malic to incorporate the teachings of a detection chamber of Lin to provide the microfluidic device further comprising an analyte detection chamber, and the microfluidic chamber coupled to the analyte detection chamber by a superparamagnetic NP channel. Doing so would utilize known microfluidic structures to improve downstream analysis of a target analyte and allow for purging of excess elements in a fluid while the target analyte is captured or trapped.
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Annotated Fig. 1b of Malic: arrows pointing to the claimed sample introduction chamber, microfluidic chamber, and sample flush reservoir.
Regarding claim 22, modified Malic further teaches a kit according to claim 16 (see above claim 16), wherein the NPs:
at least 1/3 of the NPs have a surface or subsurface coating that electrostatically or chemically repel like particles (section 2.3 teaches nanoparticles are coated with a layer of hydroxyl-terminated silica shells to reduce magnetic inter-particle interactions; thus, at least 1/3 of the nanoparticles are capable of electrostatically or chemically repelling like particles at a later time due to the silica shell); and
are surface functionalized to selectively bond to an analyte (section 2.3 teaches the nanoparticles are functionalized with anti-Listeria antibody, which is capable of selectively bonding to an analyte, e.g. Listeria).
Regarding claim 23, modified Malic further teaches the kit according to claim 22 (see above claim 22) wherein:
the microfluidic chip has a plurality of microfluidic chambers, and a plurality of fluids are provided each suspending respective NPs that are surface functionalized for selectively bonding to respective analytes (interpreted as not required due to the “or” statement following this limitation grouping); or
the magnetic field is oriented:
in a direction that minimizes an inter-pillar space between adjacent pillars of row (Fig. 4 shows the magnetic field is capable of being oriented in a direction to minimize inter-pillar space between adjacent pillars in a row, i.e. the orientation of the magnetic field captures nanoparticles between adjacent pillars along the direction of the magnetic field, thus minimizing the space between the pillars due to the presence of nanoparticles);
in a direction of one of two primitive vectors of a two-dimensional Bravais lattice defined by the at least one row (interpreted as not required due to the “or” statement); or
in a flow direction through the chamber, which is oriented at an angle between 1 and 15° with respect to one of two primitive vectors of a two-dimensional Bravais lattice defined by the at least one row (interpreted as not required due to the “or” statement).
Note that the claim 23 is interpreted as requiring one of: “wherein the microfluidic device has a plurality of microfluidic chambers, and a plurality of fluids are provided each suspending respective NP that are surface functionalized for selectively bonding to respective analytes” or “the magnetic field is oriented: in a direction that minimizes an inter-pillar space between adjacent pillars of row; in a direction of one of two primitive vectors of a two-dimensional Bravais lattice of defined by the at least one row; or in a flow direction through the chamber, which is oriented at an angle between 1 and 15° with respect to one of two primitive vectors of a two-dimensional Bravais lattice defined by the at least one row” due to the semicolon followed by the “or” limitation.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Malic in view of Ward as applied to claim 15 above, and further in view of Ham et al. (US 20060020371 A1; cited in the IDS filed 11/09/2021).
Regarding claim 18, Malic further teaches wherein the soft magnetic coating comprises a soft magnetic shell of thickness of 0.1-20 um (section 2.2 teaches a 2um thick nickel coating, i.e. soft magnetic shell; abstract teaches a nickel shell) to ensure a low remanence (abstract teaches “the very low remanence of the nickel shell”).
Modified Malic fails to teach the soft magnetic shell is composed of a nickel-based alloy the thickness and composition chosen for limiting remanence of the coating, to expedite relatively complete release of the NPs upon removal of the magnetic field.
Ham teaches an apparatus for manipulation, detection, and sorting of biological or other materials involving microfluidics and magnetic fields (abstract). Ham teaches embodiments of microcoils (paragraph [0018]) and microposts (paragraph [0019]) to create special and temporally patterned electric fields (paragraphs [0018]-[0019]). Ham teaches microcoils may comprise permalloy, i.e. a nickel based alloy, which can be easily magnetized and demagnetized depending on the current surrounding it to enhance magnetic force (paragraph [0121]).
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 the soft magnetic shell of modified Malic to incorporate the teachings of nickel based alloys of Ham (paragraph [0121]) to provide the soft magnetic shell is composed of a nickel-based alloy the thickness and composition chosen for limiting remanence of the coating, to expedite relatively complete release of the NPs upon removal of the magnetic field. Doing so would utilize known materials for magnetic manipulation of materials in a microfluidic device, as taught by Ham, to enhance magnetic force and improve ease of magnetization and demagnetization, with a reasonable expectation of success.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Malic in view of Ward as applied to claim 15 above, and further in view of Liu et al. (US 20150105287 A1; cited in the IDS filed 11/09/2021).
Regarding claim 19, Malic further teaches the support (Fig. 1h, M-chip manifold) comprises a holder for one or more additional microfluidic chips (Fig. 1h, teaches M-chip manifold comprises a “bottom microfluidic device holder”, which is structurally capable of holding a different microfluidic chip at a later time) in prescribed positions and orientations (Fig. 1h shows the M-chip manifold is structurally capable of holding a microchip in positions and orientations), in registration with the generator in a position (Fig. 1h teaches the M-chip manifold comprising a top holder, i.e. registration feature, for two permanent magnets and the top holder is capable of holding the magnets, i.e. registering the generator; thus the microfluidic device holder is capable of holding a microfluidic chip in registration with the magnets) in which one or more field lines of the magnetic field generated are at least 75% aligned with the respective polylines (Fig. 1g and 4 shows a magnetic field is at least 75% aligned with a polyline of micropillars; Fig. 3b shows a magnetic field line between micropillars are aligned).
Modified Malic fails to teach wherein the microfluidic device comprises multiple instances of the microfluidic chamber on the microfluidic chip, or on the microfluidic chip and one or more additional microfluidic chips; and the one or more additional microfluidic chips in registration with the generator in a position in which one or more field lines of the magnetic field generated are at least 75% aligned with each of the respective polylines of the respective walls of the multiple instances of the microfluidic chamber.
Liu teaches an integrated microfluidic assay comprising a microfluidic chamber (abstract; Fig. 1B). Liu teaches an apparatus comprising multiple microfluidic chambers, e.g. an array of microfluidic chambers, for high throughput treatment of samples at the same time (Fig. 1B; paragraph [0026]). Liu teaches magnets can be applied to trap magnetic beads inside a microfluidic channel (paragraph [0038]).
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 the microfluidic device of modified Malic to incorporate the teachings of multiple parallel microfluidic chambers of Liu (Fig. 1B; paragraphs [0026],[0038]) to provide wherein the microfluidic device comprises multiple instances of the microfluidic chamber on the microfluidic chip, or on the microfluidic chip and one or more additional microfluidic chips; and the one or more additional microfluidic chips in registration with the generator in a position in which one or more field lines of the magnetic field generated are at least 75% aligned with each of the respective polylines of the respective walls of the multiple instances of the microfluidic chamber. Doing so would improve throughput of fluid processing and analysis while allowing for proper aligning of magnetic fields in each chamber as desired by Malic (Fig. 3).
Response to Arguments
Applicant’s arguments, see pages 10-11, filed 09/24/2025, with respect to the claim objection have been fully considered and are persuasive. The claim objection of 07/25/2025 have been withdrawn.
Applicant's arguments, see pages 11-13, filed 09/24/2025, regarding the interpretation of limitations as intended uses, have been fully considered but they are not persuasive.
In response to applicant’s argument the office incorrectly interrupted the limitations of amended claim 15 of “where the generator's magnetic field strength, NPs, pillars, and thickness of the soft magnetic coating, ensure the kit assembled with the generator registered with the chip by the support, while the NPs are in a liquid carrier within the microfluidic chamber, enable the applied magnetic field to substantially distribute the NPs between the pillars in that at least one of the following obtains…” (emphasis added) as an intended use and fail to give them patentable weight (Remarks, pages 11-12), the examiner disagrees.
The limitations of “where the generator's magnetic field strength, NPs, pillars, and thickness of the soft magnetic coating, ensure the kit assembled with the generator registered with the chip by the support, while the NPs are in a liquid carrier within the microfluidic chamber, enable the applied magnetic field to substantially distribute the NPs between the pillars in that at least one of the following obtains…” (emphasis added) are interpreted as an intended use of the claimed microfluidic device due to the language of “enable the applied magnetic field to substantially distribute the NPs…”. Therefore, the intended uses of the claimed kit are not accorded any patentable weight, since the limitations are focused on the use of the kit comprising: the generator (e.g. applied magnetic field) with the microfluidic chip and NPs. The limitations of the distribution of the NPs between the pillars are a result of the intended use of the kit, specifically the use of the generator while NPs are in a liquid carrier within the microfluidic chamber. MPEP 2114(II) states a claim containing a recitation with respect to the manner in which a claimed apparatus is intended to be employed does not differentiate the claimed apparatus from a prior art apparatus if the prior art apparatus teaches all the structural limitations of the claim (Ex parte Masham, 2 USPQ2d 1647 (Bd. Pat. App. & Inter. 1987)). A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim.
In response to applicant’s arguments and discussion regarding In re Venezia (Remarks, pages 12-13), the examiner disagrees. It appears that applicant refers to In re Venezia to argue against indefiniteness under 35 U.S.C. 112. However, claim 15 has not been rejected under 35 U.S.C. 112(b) for indefiniteness regarding claim language that defines structural relationships between components and how they are intended to be assembled.
In response to applicant’s argument that In re Schreiber is irrelevant because it is directed to an apparatus and not a kit (Remarks, page 13) and “Kits are not subject to the same rules of interpretation as apparatus”, the examiner disagrees. Claim 15 is directed to “A kit…”. MPEP 2106.03(I) and 35 U.S.C. 101 enumerates for categories of subject matter for a patent, including processes, machines, manufactures and compositions of matter. The claimed “kit” falls within the machine category, wherein a machine is a “concrete thing, consisting of parts, or of certain devices and combination of devices.” Digitech, 758 F.3d at 1348-49, 111 USPQ2d at 1719 (quoting Burr v. Duryee, 68 U.S. 531, 570, 17 L. Ed. 650, 657 (1863)). MPEP 2114, which references In re Schreiber, discuses features of an apparatus may be recited either structurally or functionally; wherein the discussion of “an apparatus” is interpreted as referring to the limitations of a machine claim, i.e. a product, apparatus, kit. Therefore, the instant claim 15 is directed to an apparatus/machine/product claim of “A kit…” and MPEP 2114 is applicable to the claims.
Applicant's arguments, see pages 13-14, filed 09/24/2025, regarding the rejections of claim 15 under 35 U.S.C. 103 over Malic in view of Ward, have been fully considered but they are not persuasive.
In response to applicant's argument that the references fail to show certain features of the invention (Remarks, pages 13-14), it is noted that the features upon which applicant relies (i.e., “cloud wall”, “forming a cloud wall”) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
However, with the interpretation that applicant is arguing that the prior art fails to teach the “cloud wall”, which is the claimed: “a NP density at every point between two adjacent pillars of a single row is at least 50% higher than the NP density midway between two adjacent rows; a NP density at every point between two adjacent pillars of a single row is at least 50% higher than the NP density a distance normal to the polyline equal to a mean separation of the pillars; a mean NP density in inter-pillar spaces between adjacent pillars is at least 10 times higher than a mean NP density within the chamber; a magnified view from a direction in which end faces of the pillars are in view, there are no visible gaps in the NP density between adjacent pillars of any single row of the at least one row, and visible gaps across at least 80% of the chamber away from the at least one row”, the examiner disagrees. The examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, Malic teaches the claimed microfluidic chip, generator adapted to apply a magnetic field across the at least one row, NPs, and support. However, Malic fails to teach explicitly teach the generator adapted to apply a magnetic field of at least 110 kAmp/m across the at least one row, since Malic teaches a zoomed in view of magnetic fields between two magnetized pillars being about 100 kAmp/m (Fig. 3b shows magnetic fields between pillars of about 1x10^5 A/m or 100 kAmp/m; section 2.4.1 teaches a magnetic field at the center of the magnetic plate system of about 100 kA/m).
Ward teaches a microfluidic device for separation and concentration of particles in a sample (abstract; paragraph [0005]), wherein magnets are arranged adjacent to a microfluidic channel (paragraph [0005]), which is similar to Malic. Ward provides teachings and suggestions of magnetic field strengths: the magnetic field strength can be between 0.01 and 10 Tesla (paragraph [0167], converted to about 7.96-7957.75 kA/m); the system is capable of generating a magnetic field strength of at least 0.5 Tesla (paragraphs [0006], [0010], [0167]; converted to about 397. 89 kA/m). Ward provides motivation of: the magnetic field can be adjusted to influence supra and paramagnetic particles with magnetic mass susceptibility (paragraph [0168]); the use of magnets to create locally high magnetic field gradients to assist in capturing flowing magnetic particles (paragraph [0165]).
Therefore, since Ward teaches a microfluidic device with pillars to attract particles, similar to Malic, it would have been obvious to one of ordinary skill in the art to have modified the generator of Malic to incorporate the teachings of adjusting magnetic field with various magnetic field strength, such as 0.5 Tesla (about 398 kA/m) of Ward (paragraphs [0157],[0167],[0168]) to provide the generator adapted to apply a magnetic field of at least 110 kAmp/m across the at least one row. Doing so would have a reasonable expectation of successfully improving adjustability of the generator to produce a higher magnetic field strength and improve control of interaction with superparamagnetic nanoparticles as discussed by Ward (paragraphs [0165],[0168]).
Furthermore, since Malic teaches the generator capable of applying magnetic fields of about 100 kA/m (Fig. 3b shows magnetic fields between pillars of about 1x10^5 A/m or 100 kAmp/m; section 2.4.1 teaches a magnetic field at the center of the magnetic plate system of about 100 kA/m), which is merely close to the claimed range of 110 kAmp/m and Ward teaches ranges of magnetic fields of at least .1 Tesla (paragraph [0167]; 159.15 kAmp/m) and 0.5 Tesla (paragraphs [0006], [0010], [0167]; 397.89 kAmp/m) which are in the claimed range of at least 110 kAmp/m, it would have been obvious to have modified Malic to provide the generator adapted to apply a magnetic field of at least 110 kAmp/m across the at least one row (see MPEP 2144.05(I)). I.e., It would have been prima facia obvious to select the claimed range that is merely close to that of Malic and it would have been prima facia obvious to have selected known magnetic fields that are within the claimed range (see MPEP 2144.05(I)). Additionally, it would have been prima facia obvious to have selected the overlapping portion of the range (i.e. at least 159.15 kAmp/m or at least 397.89 kAmp/m) from the taught range of at least 159.15 kAmp/m or 397.89 kAmp/m (Ward; paragraphs [0006], [0010], [0167]) (In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); see MPEP 2144.05 (I)).
Therefore, the apparatus of modified Malic is identical to the presently claimed structure as discussed above. Since modified Malic discloses the claimed “microfluidic chip”, “generator”, and “support” as claimed and therefore, would have the ability to perform the intended uses and functional limitations in the claim. See MPEP 2112.01 (I). Moreover, modified Malic arrangement of the claimed pillars, the generator adapted to apply a magnetic field strength of at least 110 kAmp/m, and support is structurally capable of performing the claimed limitations of “where the generator's magnetic field strength, NPs, pillars, and thickness of the soft magnetic coating, ensure the kit assembled with the generator registered with the chip by the support, while the NPs are in a liquid carrier within the microfluidic chamber, enable the applied magnetic field to substantially distribute the NPs between the pillars in that at least one of the following obtains…”, i.e. forming a cloud wall. For example, Malic, Fig. 4, center pictures, shows the magnetic field strength, NPs, pillars with magnetic coatings structurally capable of allowing every point between two adjacent pillars of a row to have at least 50% higher NP density than the NP density between two adjacent rows, i.e. the row above or below, at a later time; i.e. depending on the amount of NPs, size of the NPs, and/or length of time, the NPs are capable of being distributed as claimed. If applicant desires to claim the specific distribution of the NPs, it is suggested to positively