Detailed Action
This is a Final Office action based on application 16/919,134 filed on July 2, 2020. The application is a CON of PCT/IL2019/050011 filed January 2, 2019, and claims priority to US provisional application 62/612,757 filed January 2, 2018.
Claims 1-26 are pending, claims 16-24 are withdrawn, and claims 1-15 and 25-26 have been fully considered.
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 .
Status of the Rejection
Applicant’s amendment has overcome the §102 rejection of record
New §103 grounds of rejection are established
New §112(a) grounds is applied to claim 1 and its dependents
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-15 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Particularly, the reason we consider claim 1 to define unsupported subject matter is because the claim text Applicant uses to describe the shape of the heater (“extending along a directional axis and curving about said axis”) encompasses a broad set of shapes, of which the originally filed disclosure only actually provides support for a subset. There is no text describing the curved shape of the heater shape in the instant specification; support for the amendment is therefore drawn from the figures which show a thin film resistive heater with a serpentine shape (this is shown in several figures and is perhaps most clearly visible in figures 13(b),(d)). However, the claim language “extending along a directional axis and curving about said axis” encompasses many other shapes, such as cylinders, spirals, arcs, an helices, which the original disclosure does not provide support for. Applicant’s amendment therefore introduces into claim 1 a subject matter that is not commensurate in scope with the support provided by the specification.
To give an example, “Krishnamoorthy” (US 7,604,394 B2 to Krishnamoorthy et al) discloses electrothermal heaters operable to stir fluid in a microfluidic device. As shown in figure 8 of Krishnamoorthy, the heaters 12, 14 are extending along the axis of a cylindrical microchannel and are curved about the cylinder axis. This heater shape fits in the scope of the claim language despite being very different than any shape
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applicant’s disclosure provides support for.
Reproduction of figure 8 of Krishnamoorthy
Claims 2-15 are rejected by extension because they depend from claim 1.
This ground of rejection could be overcome by amending the recited heater shape (“extending along a directional axis and curving about said axis”) to more accurately reflect the shape disclosed in the specification. Note that new claim 26 instead describes the heater shape as a “serpentine geometry”. This narrower recitation of the heater shape is commensurate in scope with the heater as illustrated in Applicant’s figures, and is not considered new matter. One way claim 1 could be amended that would be acceptable under §112(a) is:
“ ... the heater extending along a directional axis and curving in a serpentine geometry about said axis”
Other manner of recitation is possible too. Appropriate correction is required.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1, 2, 6, 14, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Park et al ("Induced-charge electrokinetics, bipolar current, and concentration polarization in a microchannel–Nafion-membrane system", Physical Review E, volume 93, article #062614, pages 1-10 (2016)), in view of Williams (“Enhanced electrothermal pumping with thin film resistive heaters”, Electrophoresis, 34, 1400-1406 (2013)), in further view of Handique (US 6,692,700 B2).
Regarding claim 1, Park teaches a microchannel-membrane device (pg 1 abstract, "a microchannel-membrane interface device"; the device is illustrated in pg 2 figure 1) comprising:
a microchannel ("microchannel" in pg 2 figure 1a);
first and second electrodes for generating a concentration-polarization layer (pg 3 left column para 2, "Two platinum wire electrodes ... inserted within each reservoir"; pg 2 figure 1, first and second electrodes are located at inlet holes, near the two points labeled "microchannel" in figure 1a; these electrodes supply the current Itot into the microchannel, which drives ionic current through the Nafion membrane segment. Ionic current through the permselective Nafion medium thereby generates a concentration-polarization layer, as discussed in pg 1 left column para 1; per pg 5 left column para 2 - pg 6 right column para 3, a concentration polarization layer is generated);
said microchannel extending through at least said first electrode and between the first and second electrodes (as shown in pg 2 figure 1a, the microchannel extends through the first electrode and between the first and second electrode), the microchannel having a predetermined depth (per pg 2 left column para 4, the microchannel has a depth of 45 µm);
an ionic permselective medium across said microchannel between said first and second electrodes (pg 2 figure 1a, "Nafion nanoslot"; pg 2 left column para 4 - right column para 1); and
an electrically insulated induction electrode array embedded at a lower side of said microchannel on a first side of said permselective medium (pg 2 figure 1a, "electrode array"; pg 2 left column para 4, a linear array of ten Cr-Au electrodes is embedded underneath the microchannel, insulated from the channel by SiO2 dielectric coating; as disclosed in pg 1 right column para 2 - pg 2 left column para 1 and in pg 6 right column para 4 - pg 8 right column para 1, said linear electrode array is operable to induce alternating-current electro-osmosis (ACEO) in the solution in the microchannel above the electrode array, resulting in the formation of vortices that stir the fluid; pg 4 right column para 1 and pg 5 figure 5(b), the SiO2 coating over the electrodes is sufficient electrical insulation to block Faradaic reactions between the electrode and fluid in the microchannel; pg 6 left column para 1, “results demonstrated the optimal thickness of the SiO2 layer (i.e., 50-nm-thick SiO2), which can suppress the Faradaic reaction yet still support the vortex induced by ICEO”), said electrodes extending along a directional axis (as can be seen in pg 2 figure 1(a) and 1(b), the electrodes extend along the vertical axis of the image).
The stated function of Park’s induction electrode array is to induce a vortex that stirs the concentration polarization depletion region by way of an ICEO or ACEO induced vortex (pg 1 abstract; pg 8 right column para 1, “Conclusion ...”). Park’s disclosed induction electrodes read on claimed "at least one heater ... said at least one heater being controllable to generate an electrothermal-induced vortex, due to induced electrothermal forcing, by common application of an electric field along with temperature gradients induced by said at least one heater", because they are capable of being used to heat fluid in the microchannel, and of being used to generate an electrothermal-induced vortex due to induced electrothermal forcing, by common application of an electric field along with temperature gradients induced by said at least one heater. Park discloses using the electrodes to apply electric field to fluid in the microchannel, thereby driving fluid motion by AC electro-osmosis (ACEO) (pg 6 right column para 4 - pg 8 right column para 1), and, as discussed in pg 5-7 of the previous Office Action, they inherently possess the capability of being controlled in a manner that would heat the fluid and generate an electrothermal-induced vortex (see pg 5-7 of the Office Action of June 11, 2025).
The limitation "said heater having a characterized relationship between activation thereof and ionic concentration" does not describe a structural feature that can be relied upon to distinguish the claimed structure from Park’s structure. Apparatus claims are limited only by the actual physical structure of the recited apparatus, and are not limited by the way in which the structure is characterized or understood. Therefore a prior art reference which discloses every physical structural feature of the claimed apparatus will read on the claims even if the prior art does not disclose a characterized relationship between activation of the structure and ionic concentration. See MPEP 2112(I-II) and 2114.
However the claimed heaters are structurally distinct from Park’s induction electrodes because, while Park’s electrodes do extend along a directional axis (Park pg 2 figure 1(a)-(b)), Park does not teach or imply the feature of wherein the heater is curving about that axis.
Williams teaches that embedded electrodes in a microfluidic device can be used to drive electrokinetic movements of the fluid therein, by both AC electroosmosis (ACEO) and/or electrothermal mechanisms (pg 1400 “Introduction ...”; pg 1402 figures 1-2 illustrating Williams’s device), consistent with our finding that Park’s embedded electrodes, which Park describes as ACEO electrodes, are capable of being used as heaters to drive electrothermal vortex formation. Williams teaches that electrothermal pumping is more effective than ACEO for biologically relevant fluid conductivities (pg 1400 left column para 1 – right column para 1). Williams goes on to say that such an electrothermal device can be improved upon if, rather than using induced current in the fluid itself to provide the localized Joule heating required for electrothermal pumping, the device instead used an embedded resistive heating wire (pg 1400 right column para 2-4). One benefit of using a heating coil rather than induced heating of the fluid, per Williams’s teachings, is that the effectiveness of the heater is independent of the fluid conductivity, so electrothermal pumping can be performed more effectively on low-conductivity fluids (Williams at pg 1400 right column para 2-4; pg 1404 left column para 2). Williams discloses structure of a microfluidic device having at least one electrically insulated heated embedded at a lower side of said microchannel (pg 1402 figures 1-2), and discloses a characterized relationship between activation of the heater and ionic concentration (pg 1404 Table 1, figure 5).
Handique discloses a thin film resistive heater structure for use in a microfluidic device, wherein the heater is embedded at a lower side of a microchannel and electrically insulated therefrom (figure 1, resistive heater 140 is embedded in glass base 130 beneath oxide layer 150; “lower substrate 125 includes a glass base 130 and an oxide layer 150. Within oxide layer 150, resistive heaters 140 and electric leads 160 are formed”), wherein the heater extends along a directional axis and curves in a serpentine fashion about said axis (as seen in figures 1, 5, 10, 13, 16; note that figure 1 illustrates a conventional heater of the prior art, and figures 5, 10, 13, 16 depict Handique’s inventive heater, and the recited feature in present in both).
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify Park’s device by substituting, in place of the induction electrodes, a thin film resistive heater as taught in Williams, because Park is specifically directed to using their induction electrodes specifically for electrokinetic stirring of a concentration polarization depletion region, i.e. a region of a microfluidic device in which ion concentration is very low; and, Williams teaches that an embedded resistive heater has a heating power that is independent of the fluid’s ion concentration, which makes it more effective than induction electrodes for electrothermal heating and transport especially in fluids having low ionic conductivity (Williams at pg 1400 right column para 2-4; pg 1404 left column para 2). Furthermore it would have been obvious, when implementing the thin film resistive heater in Park’s device, to use a resistive heater that extends along a directional axis and curves in a serpentine fashion about said axis, based on Handique’s teaching that this is a suitable shape for a thin film resistive heater in a microfluidic device. The simple substitution of one known element for another (i.e., a resistive heater in place of an induction heater) is likely to be obvious when predictable results are achieved (i.e., controllable heater output for electrothermal stirring of the adjacent fluid channel, independent of the local ionic concentration of the fluid) [MPEP § 2143(B)]. Furthermore, the selection of a known component (i.e. a thin film with 2D serpentine shape as known from Handique), based on its suitability for the intended use, is within the ambit of one of ordinary skill in the art [MPEP § 2144.07].
Regarding claim 2, Park in view of Williams and Handique renders obvious the microchannel-membrane device of claim 1, and Park further teaches their at least electrically insulated one heater comprises an array of electrically insulated heaters embedded below said microchannel at intervals along said first side of said permselective medium (per pg 2, left column para 4 - right column para 1 and figure 1a-b, the at least one heating electrode is a linear array of ten electrodes, spaced at an interval of 40 µm, embedded under the microchannel on a first side of the permselective Nafion membrane). Park teaches that, by placing an array of individually addressable electrodes, and selectively activating a subset of the array, they are able to achieve spatial control over an ICEO vortex and thereby control the location where the concentration polarization layer is disrupted by the vortex-induced stirring (pg 7-8 and figures 10, 11, 13).
Williams similarly teaches that, when resistive heating elements are used as the heaters, the device may be configured with an array of individually addressable heaters, and this would allow the operator to control the spatial location of the electrothermal transport effect (pg 1405 left column para 3).
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention, when modifying Park’s device in view of Williams, to replace the array of induction heating electrodes with an array of resistive heaters as disclosed in Williams rather than with a single heater, thereby to retain the feature (already present in Park) of wherein the heaters can be addressed individually to control the spatial location of an induced vortex.
Regarding claim 6, Park in view of Williams and Handique renders obvious the microchannel-membrane device of claim 1, and Park further teaches their at least one heater comprises an array of heaters embedded below said microchannel at intervals along said first side of said permselective medium (per pg 2, left column para 4 - right column para 1 and figure 1a-b, the at least one heating electrode is a linear array of ten electrodes, spaced at an interval of 40 µm, embedded under the microchannel on a first side of the permselective Nafion membrane) and said at least one heater or array comprises a dielectric coating, thereby to provide an electrical insulation layer (pg 2 left column para 4, the heater array comprises a SiO2 dielectric coating separating the heating electrodes from liquid in the microchannel). Park teaches that, by placing an array of individually addressable electrodes, and selectively activating a subset of the array, they are able to achieve spatial control over an induced vortex and thereby control the location where the concentration polarization layer is disrupted by the vortex-induced stirring (pg 7-8 and figures 10, 11, 13).
Williams similarly teaches that, when resistive heating elements are used as the heaters, the device may be configured with an array of individually addressable heaters, and this would allow the operator to control the spatial location of the electrothermal transport effect (pg 1405 left column para 3).
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention, when modifying Park’s device in view of Williams, to replace the array of induction heating electrodes with an array of resistive heaters as disclosed in Williams rather than with a single heater, thereby to retain the feature (already present in Park) of wherein the heaters can be addressed individually to control the spatial location of an induced vortex.
Regarding claim 14, Park in view of Williams and Handique renders obvious the microchannel-membrane device of claim 1, and Park further teaches said ion permselective medium comprises a Nafion membrane (pg 2 left column para 4 - right column para 1; pg 2 figure 1).
Regarding claim 15, Park in view of Williams and Handique renders obvious the microchannel-membrane device of claim 1, and Park further teaches the microchannel extends between the first and second electrodes (as shown in pg 2 figure 1a).
Claims 3-5 are rejected under 35 U.S.C. 103 as being unpatentable over Park as applied to claim 1 above, in view of Lu et al ("Long-range electrothermal fluid motion in microfluidic systems", International Journal of Heat and Mass Transfer, volume 98, pages 341-349 (2016)). Evidentiary support for the rejection of claim 4 is provided by Ng.
Regarding claim 3, Park in view of Williams and Handique renders obvious the microchannel-membrane device of claim 1, but Park does not teach the predetermined depth of the microchannel is greater than 0.3mm or 0.4mm, or about 1mm, or 1mm, or 1.5mm.
Lu studies fluid vortices induced by AC electrothermal flow in a microchannel with embedded electrodes (pg 341 abstract, pg 342 left column para 2 - right column para 1, pg 343 figure 1). Lu teaches that length scale of fluid mixing by AC electrothermal effect is dependent on the predetermined depth of the microchannel; long-range fluid is observed at a channel depth of 0.3 mm (pg 347-348 figures 4-5), is observed to increase as channel depth increases over the range 0.3 to 0.8 mm (pg 347 figure 4, pg 348 figure 6), and such fluid motion is suppressed when the channel depth is less than 0.3 mm (pg 345 right column para 4 - pg 346 left column para 1; pg 347 figure 4).
It would have been obvious to a person having ordinary skill in the art at the time of the invention to modify the device of Park by defining the depth to be greater than 0.3 mm as taught in Lu, because Park is directed to using electrokinetically induced fluid vortices to stir fluid in the microchannel, and Lu teaches that long range ACET fluid motions that would be capable of stirring the fluid are suppressed when the channel depth is less than 0.3 mm.
Regarding claim 4, Park in view of Williams, Handique, and Lu renders obvious the microchannel-membrane device of claim 3. Park further teaches wherein said at least one electrically insulated heater comprises an array of heaters embedded below said microchannel at intervals along said first side of said permselective medium (per pg 2, left column para 4 - right column para 1 and figure 1a-b, the at least one heating electrode is a linear array of ten electrodes, spaced at an interval of 40 µm, embedded under the microchannel on a first side of the permselective Nafion membrane) and electrically insulated heaters of said array are separately controllable to define heating locations along said microchannel (pg 7 figures 10-11, Park defines the location of ACEO effect by selecting which heaters of the array AC is applied to, ergo the heaters are separately controllable). Park further teaches the heaters are controllable to generate an electro-osmosis-induced vortex, therewith to limit growth of a diffusion length to said first location on said first side, said first side being a depletion side of said membrane (pg 6 right column para 4 - pg 8 left column para 2; pg 7 figure 10 and associated caption). It is contended that Park's heaters therefore possess the feature of being controllable to generate an electrothermal-induced vortex.
Evidentiary support is found in Ng. Ng discloses a similar microfluidic device which uses AC field, applied via embedded electrodes, to generate vortices that stir fluid via AC electroosmosis (ACEO). Ng teaches that the same electrodes that are used in an AC electroosmosis (ACEO) regime can also be used to induce Joule heating in fluid and thereby generate stirring vortices in an AC electrothermal (ACET) flow regime (pg 807 right column para 3 - pg 808 right column para 1). The occurrence of either the ACEO or ACET flow regime is determined by the frequency and voltage of the applied AC potential as well as by physical properties of the fluid being acted upon (Ng pg 803 right column para 2-3). Therefore it follows that Park's heater electrode array, with which Park demonstrates controlling to generate of fluid vortices in the ACEO flow regime, is inherently capable of also being controlled to generate vortices in the ACET regime.
The functional feature inherently present in Park, wherein the electrodes are operable to induce an electrothermal vortex that limits growth of the concentration polarization depletion layer to a particular heating location, would apparently be retained in Park’s device if the induction heaters were modified into thin-film resistive heating elements as suggested by Williams and Handique, because Williams teaches that the heat provided by the resistive heaters in an electrothermal device is a direct substitute for the Joule heating by current induced in the fluid (pg 1403-1404 (“Results and discussion ... The nature of both temperature fields appears similar, but the thin film heater’s normalized temperature field produces sharper gradients closer to the electrode ... electrothermal flow from thin film heating alone is greater than for Joule heating alone”; pg 1404 figure 4 shows vortices are formed in the fluid flow field by either method), and Williams similarly teaches placing an array of individually addressable heaters under the microchannel in order to control the location of the electrothermal-induced flow (pg 1405 left column para 2-3).
Regarding claim 5, Park in view of Williams, Handique, and Lu renders obvious the microchannel-membrane device of claim 4. Park further teaches said electrically insulated heaters are dynamically controllable to change the location at which the alternating field is applied, and thereby to move an EO-induced vortex along said microchannel and alter the length of the concentration-polarization depletion zone (pg 7 figures 10-11). It follows that the heaters would be likewise controllable when operated as heaters in the ACET rather than ACEO regime.
The functional feature inherently present in Park, wherein the electrodes are operable to induce an electrothermal vortex that limits growth of the concentration polarization depletion layer to a particular heating location, would apparently be retained in Park’s device if the induction heaters were modified into thin-film resistive heating elements as suggested by Williams and Handique, because Williams teaches that the heat provided by the resistive heaters in an electrothermal device is a direct substitute for the Joule heating by current induced in the fluid (pg 1403-1404 (“Results and discussion ... The nature of both temperature fields appears similar, but the thin film heater’s normalized temperature field produces sharper gradients closer to the electrode ... electrothermal flow from thin film heating alone is greater than for Joule heating alone”; pg 1404 figure 4 shows vortices are formed in the fluid flow field by either method), and Williams similarly teaches placing an array of individually addressable heaters under the microchannel in order to control the location of the electrothermal-induced flow (pg 1405 left column para 2-3).
Claims 7-8 are rejected under 35 U.S.C. 103 as being unpatentable over modified Park as applied to claim 1 above, in view of Wang et al ("Pre-binding dynamic range and sensitivity enhancement for immuno-sensors using nanofluidic preconcentrator", Lab on a Chip, volume 8, pages 392-394 (2008)).
Regarding claim 7, Park in view of Williams and Handique renders obvious the microchannel-membrane device of claim 1. Park teaches that the heater could be controlled to generate a vortex that limits the spatial extent of the depletion portion of the concentration-polarization layer (pg 6 right column para 4 - pg 8 left column para 2; pg 7 figure 10 and associated caption). Park teaches that such a means of controlling the position of the end of the depletion layer would be useful in the context of a device that comprises a preconcentrated biomolecule plug positioned at the end of the depletion layer, because it would enable spatiotemporal control of the position of the preconcentrated biomolecule plug (pg 2 left column para 1). However, Park does not disclose that their device actually contains such a preconcentrated plug of target molecules.
Wang teaches a microchannel device (pg 392 right column para 2, "integrating a standard bead-based immunoassay with a nanofluidic preconcentrator in a microfluidic device format"; pg 393 figure 1) comprising electrodes and an ionic permselective medium for generating a concentration-polarization layer (pg 393 figure 1, the "nanofluidic channel" region defines an ionic permselective medium, and a potential bias is applied across the nanofluidic channel to generate an ion depletion region via concentration polarization effect; pg 392 right column para 4 - pg 393 left column para 1), and a preconcentrated plug of target biomolecules formed at a depletion end of a diffusion length (pg 393 figure 1b, a preconcentrated plug of "trapped biomolecule" is formed at the edge of the ion depletion region; pg 39 right column para 2 - pg 393 left column para 1). Wang further teaches the microchannel device comprises a bead-based immunoassay (pg 393 left column para 2 - right column para 2). Wang teaches that such forming of a preconcentrated plug of biomolecules at the edge of the ion depletion region is advantageous, because increasing the concentration of the biomolecules allows those biomolecules to be detected more effectively by the immunoassay (pg 393 left column para 2 - pg 394 right column para 1).
It would have been obvious to a person having ordinary skill in the art at the time of the invention to further modify Park to incorporate a concentrated plug of target biomolecules at the edge of the depletion region of the concentration polarization layer, as taught in Wang, in order to attain a device that can manipulate the position of a concentrated plug of target biomolecules as taught in Park (pg 2 left column para 1). Such modification would have the predictable result of increasing the local concentration of biomolecules, which would effectively improve the detection sensitivity of an assay for detecting those biomolecules. Furthermore, the claimed limitations are obvious because all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results [MPEP 2143(A)].
Regarding claim 8, Park in view of Williams, Handique, and Wang renders the microchannel-membrane device of claim 7 obvious. Park further teaches the at least one heater or array is controllable to locate said preconcentrated target biomolecules by manipulating the location of the edge of the ion depletion region (pg 2 left column para 1).
Wang further teaches that the preconcentrated plug of target biomolecules is controlled so as to locate the biomolecules on the surface of a colloid within the microchannel (pg 392 right column para 4 - pg 393 right column para 2; figure 2. Streptavidin-coated beads are positioned in the microchannel, held in place by a narrowing of the channel. When bias is applied across the permselective medium to form an ion depletion region, then the preconcentrated plug of biomolecules is positioned at the edge of the depletion region, a position which overlaps the location of the beads (as shown in figure 2(b))).
It follows that, in modifying the device of Park to incorporate the teachings of Wang, one would obviously arrange the heaters, which control the position of the ion depletion region edge, such that they are controllable to locate the ion depletion region edge proximate to a colloid within said channel, as Wang does, so that the preconcentrated biomolecules in turn are located at the surface of the colloid and are thereby able to bind with the colloid for the purpose of performing an immunoassay as taught in Wang.
Claims 9-13 are rejected under 35 U.S.C. 103 as being unpatentable over Park, Williams, Handique, and Wang as applied to claim 8 above, in further view of Auerswald et al (US 2006/0102482 A1).
Regarding claim 9, Park in view of Williams, Handique, and Wang renders the microchannel-membrane device of claim 8 obvious. Wang further teaches the device is configured to perform an immunoassay using functionalized microparticles (pg 393 left column para 2 - right column para 2, "To integrate the preconcentrator with an immunoassay ... With this device, bead-based immune-sensing can be realized ..."; pg 393 figure 2). However, Park and Wang do not disclose that the device is configured to apply one or more forces selected from dielectrophoresis, manetophoresis, optophoresis, electrophoresis, thermophoresis, and diffusiophoresis, with functionalized micro- or nano-particles, in order to control their manipulation, thereby to perform an immunoassay.
Auerswald teaches a microchannel device for performing an immunoassay (para [0020]-[0026]), comprising a microchannel (figure 2, microchannel 21; para [0054]), and electrodes embedded beneath the microchannel (figure 2, electrodes 24; para [0052], "interdigitated microelectrodes 24"). The device is configured to apply dielectrophoresis forces to functionalized microparticles, in order to control their manipulation (para [0031]-[0032]; para [0055], "beads will be retained at the electrodes by positive dielectrophoresis), thereby to perform an immunoassay (para [0033]-[0034]; para [0056]-[0060]). Auerswald teaches that such a device, which applies a dielectrophoresis force to retain the functionalized beads in a desired reaction region, is advantageous because it allows beads to be temporarily held in place for the purpose an assay, then released and washed away once the assay is finished, thereby allowing the microfluidic assay device to be reused with fresh beads (para [0022]); it does so without requiring the use of microfabricated physical barriers or relatively bulky magnetic field generating apparatus (para [0021]); and the resulting system is more versatile than physical / magnetic retention means, because the ability of the dielectrophoresis electrodes to retain a bead is not particularly limited by the bead's size or composition (para [0023]).
It would have been obvious to a person having ordinary skill in the art at the time of the invention to modify the device of Park and Wang by configuring the device to use dielectrophoresis force to manipulate the microparticles used in the immunoassay, rather than retaining beads with a physical barrier as disclosed in Wang (pg 393, left column para 2 - right column para 2 and figure 2), in order to create a versatile microfluidic immunoassay platform that is readily reusable and is compatible with a wide variety of immunosorbent beads, as taught in Auerswald (para [0020]-[0025]). All the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results. The simple substitution of one known element for another (i.e., a dielectrophoretic bead trap in place of a physical barrier bead trap) is likely to be obvious when predictable results are achieved (i.e., effective trapping and release of probe beads for a microfluidic immunoassay) [MPEP § 2143(B)].
Regarding claim 10, Park, Williams, Handique, Wang, and Auerswald render obvious the microchannel-membrane device of claim 9, and Wang teaches the probes are configured to operate via microparticle-based antibody immobilization (pg 393 left column para 2 - right column para 2, probes comprise GFP antibody or R-phycoerythrin antibody, immobilized by attaching to polystyrene microparticles).
Regarding claim 11, Park, Williams, Handique, Wang, and Auerswald render obvious the microchannel-membrane device of claim 10, and Auerswald teaches that the dielectrophoresis manipulation of microparticles is implemented as an array of interdigitated electrodes for trapping said microparticles (figure 2, interdigitated electrodes 24; para [0054]-[0055]).
Regarding claim 12, Park, Williams, Handique, Wang, and Auerswald render obvious the microchannel-membrane device of claim 11, and Auerswald teaches said interdigitated electrodes are pairwise addressable to carry out dielectrophoresis to trap microparticles (para [0031]-[0032], [0054]-[0055]), and also teaches wherein said interdigitated electrodes are further controllable by said pairwise addressing to release said microparticles after entrapment for further analysis (para [0022], [0026]; claims 28-35).
Regarding claim 13, Park, Williams, Handique, Wang, and Auerswald render obvious the microchannel-membrane device of claim 12, and Wang teaches the immunoassay is bead-based (pg 392 right column para 2, "This is demonstrated by integrating a standard bead-based immunoassay with a nanofluidic preconcentrator in a microfluidic device format").
Claim 25 is rejected under 35 U.S.C. 103 as being unpatentable over Park in view of Williams and Wang.
Regarding claim 25, Park teaches a microchannel-membrane device (pg 1 abstract, "a microchannel-membrane interface device"; the device is illustrated in pg 2 figure 1) comprising:
a microchannel ("microchannel" in pg 2 figure 1a);
first and second electrodes for generating a concentration-polarization layer (pg 3 left column para 2, "Two platinum wire electrodes ... inserted within each reservoir"; pg 2 figure 1, first and second electrodes are located at inlet holes, near the two points labeled "microchannel" in figure 1a; these electrodes supply the current Itot into the microchannel, which drives ionic current through the Nafion membrane segment. Ionic current through the permselective Nafion medium thereby generates a concentration-polarization layer, as discussed in pg 1 left column para 1; per pg 5 left column para 2 - pg 6 right column para 3, a concentration polarization layer is generated);
said microchannel extending through at least said first electrode and between the first and second electrodes (as shown in pg 2 figure 1a, the microchannel extends through the first electrode and between the first and second electrode), the microchannel having a predetermined depth (per pg 2 left column para 4, the microchannel has a depth of 45 µm);
an ionic permselective medium across said microchannel between said first and second electrodes (pg 2 figure 1a, "Nafion nanoslot"; pg 2 left column para 4 - right column para 1); and
an induction electrode array embedded at a lower side of said microchannel on a first side of said permselective medium (pg 2 figure 1a, "electrode array"; pg 2 left column para 4, a linear array of ten Cr-Au electrodes is embedded underneath the microchannel, separated from the channel by SiO2 dielectric coating; as disclosed in pg 1 right column para 2 - pg 2 left column para 1 and in pg 6 right column para 4 - pg 8 right column para 1, said linear electrode array is operable to induce alternating-current electro-osmosis (ACEO) in the solution in the microchannel above the electrode array, resulting in the formation of vortices that stir the fluid) wherein the induction electrode array is electrically insulated (pg 2 left column para 4, Cr-Au electrodes are embedded underneath the microchannel and insulated from the channel by SiO2 dielectric coating; pg 4 right column para 1 and pg 5 figure 5(b), the SiO2 coating over the electrodes is sufficient electrical insulation to block Faradaic reactions between the electrode and fluid in the microchannel; pg 6 left column para 1, “results demonstrated the optimal thickness of the SiO2 layer (i.e., 50-nm-thick SiO2), which can suppress the Faradaic reaction yet still support the vortex induced by ICEO”).
Park's induction electrodes read on claimed "at least one heater ... said at least one heater being controllable to generate an electrothermal-induced vortex, due to induced electrothermal forcing, by common application of an electric field along with temperature gradients induced by said at least one heater", because they are capable of being used to heat fluid in the microchannel, and of being used to generate an electrothermal-induced vortex due to induced electrothermal forcing, by common application of an electric field along with temperature gradients induced by said at least one heater. Park discloses using the electrodes to apply electric field to fluid in the microchannel, thereby driving fluid motion by AC electro-osmosis (ACEO) (pg 6 right column para 4 - pg 8 right column para 1), a process which inherently results in heating of the fluid, and there is no apparent structural difference between the electrode array of Park, and an electrode array that is controllable to generate an electrothermal-induced vortex, as recited.
The stated function of Park’s induction electrode array is to induce a vortex that stirs the concentration polarization depletion region by way of an ICEO or ACEO induced vortex (pg 1 abstract; pg 8 right column para 1, “Conclusion ...”). Park’s disclosed induction electrodes read on claimed "at least one heater ... said at least one heater being controllable to generate an electrothermal-induced vortex, due to induced electrothermal forcing, by common application of an electric field along with temperature gradients induced by said at least one heater", because they are capable of being used to heat fluid in the microchannel, and of being used to generate an electrothermal-induced vortex due to induced electrothermal forcing, by common application of an electric field along with temperature gradients induced by said at least one heater. Park discloses using the electrodes to apply electric field to fluid in the microchannel, thereby driving fluid motion by AC electro-osmosis (ACEO) (pg 6 right column para 4 - pg 8 right column para 1), and, as discussed in pg 16-17 of the previous Office Action, they inherently possess the capability of being controlled in a manner that would heat the fluid and generate an electrothermal-induced vortex (see pg 5-7 of the Office Action of June 11, 2025).
However the claimed heaters are structurally distinct from Park’s induction electrodes because, while Park’s electrodes are coated with a coating comprising at least one electrical insulating layer (pg 2 left column para 4, a linear array of ten Cr-Au electrodes is embedded underneath the microchannel, insulated from the channel by SiO2 dielectric coating; pg 4 right column para 1 and pg 5 figure 5(b), the SiO2 coating over the electrodes is sufficient electrical insulation to block Faradaic reactions between the electrode and fluid in the microchannel), Park does not teach said coating being at least half a micron in thickness.
Williams teaches that embedded electrodes in a microfluidic device can be used to drive electrokinetic movements of the fluid therein, by both AC electroosmosis (ACEO) and/or electrothermal mechanisms (pg 1400 “Introduction ...”; pg 1402 figures 1-2 illustrating Williams’s device), consistent with our finding that Park’s embedded electrodes, which Park describes as ACEO electrodes, are capable of being used as heaters to drive electrothermal vortex formation. Williams teaches that electrothermal pumping is more effective than ACEO for biologically relevant fluid conductivities (pg 1400 left column para 1 – right column para 1). Williams goes on to say that such an electrothermal device can be improved upon if, rather than using induced current in the fluid itself to provide the localized Joule heating required for electrothermal pumping, the device instead used an embedded resistive heating wire (pg 1400 right column para 2-4). One benefit of using a heating coil rather than induced heating of the fluid, per Williams’s teachings, is that the effectiveness of the heater is independent of the fluid conductivity, so electrothermal pumping can be performed more effectively on low-conductivity fluids (Williams at pg 1400 right column para 2-4; pg 1404 left column para 2). Williams discloses structure of a microfluidic device having at least one electrically insulated heated embedded at a lower side of said microchannel (pg 1402 figures 1-2), said at least one heater being coated with a coating comprising an electrical insulating layer of at least half a micron in thickness (pg 1402 figure 1 and right column para 2, “The heater is embedded in the glass substrate, separated from the above pumping electrodes with a 1.0-µm-thick electric insulation”).
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify Park’s device by substituting, in place of the induction electrodes, the thin film resistive heater structure as taught in Williams, because Park is specifically directed to using their induction electrodes specifically for electrokinetic stirring of a concentration polarization depletion region, i.e. a region of a microfluidic device in which ion concentration is very low; and, Williams teaches that an embedded resistive heater has a heating power that is independent of the fluid’s ion concentration, which makes it more effective than induction electrodes for electrothermal heating and transport especially in fluids having low ionic conductivity (Williams at pg 1400 right column para 2-4; pg 1404 left column para 2). The simple substitution of one known element for another (i.e., a resistive heater in place of an induction heater) is likely to be obvious when predictable results are achieved (i.e., controllable heater output for electrothermal stirring of the adjacent fluid channel, independent of the local ionic concentration of the fluid) [MPEP § 2143(B)].
The structure of Park's device further differs from the structure of the claimed device in that Park defines a single microchannel extending between the first and second electrodes, and locates the second electrode in that microchannel. Park fails to disclose the second electrode being located in a second, side microchannel, as claimed.
Wang teaches a microchannel device (pg 392 right column para 2, "integrating a standard bead-based immunoassay with a nanofluidic preconcentrator in a microfluidic device format"; pg 393 figure 1) comprising first and second electrodes and an ionic permselective medium for generating a concentration-polarization layer (pg 392 right column para 4 - pg 393 left column para 1; pg 393 figure 1, the "nanofluidic channel" region defines an ionic permselective medium, and a potential bias is applied across the nanofluidic channel to generate an ion depletion region via concentration polarization effect; for purpose of this claim rejection, the electrode located at the left end of the "microfluidic sample channel" and biased at +30 V, is considered the "first electrode" and the grounded electrode at an end of the "microfluidic buffer channel" is considered the "second electrode", see examiner's annotation of Wang figure 1 below), a first microchannel extending through the first electrode and extending between said first and second electrodes ("microfluidic sample channel" in Wang pg 393 figure 1; see examiner's annotation), a second, side microchannel in which the second electrode is located ("microfluidic buffer channel" in Wang figure 1; see examiner's annotation), and wherein the ionic permselective medium is disposed across said microchannel between the first and second electrodes (pg 393 figure 1, nanofluidic channels are arranged across the microfluidic sample channel (the first microfluidic channel)).
Examiner's annotation on Wang figure 1
Wang teaches that their device has utility for an immunoassay (pg 393 left column para 2 - right column para 2), in which a biomolecule is introduced to, flowed through, and collected from the first microchannel while the first and second electrodes and ion-permeable medium are used to generate a concentration-polarization layer that extends into the space of the first microchannel (pg 392 right column para 3 - pg 394 left column para 1). Since the first microchannel branches to a side channel that contains the second electrode, rather than the second electrode being located in the first microchannel, the apparent effect is that charged biomolecules introduced into the first microchannel can be influenced by the concentration polarization layer (see "trapped biomolecule" at the concentration polarization front in Wang figure 1b) but are not forced to flow through the ionic selective media into the second side microchannel. Wang teaches their device is effective to preconcentrate large analytes such as proteins to increase the sensitivity of an assay (pg 392 right column para 4 - pg 394 right column para 1).
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the structure of Park's device by introducing a second, side microchannel and placing the second electrode in the side channel, based on Wang's disclosure of such a structure and Wang's teaching that a device structured this way has useful functions e.g. preconcentration of charged analytes for a sensitive assay. The claimed limitations are obvious because all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results [MPEP 2143(A)].
Claim 26 is rejected under 35 U.S.C. 103 as being unpatentable over Park, Williams, and Wang as applied to claim 25 above, in further view of Handique.
Regarding claim 26, Park, Williams, and Wang render obvious the device of claim 25, but Park does not disclose the at least one electrically insulated heater comprises a serpentine geometry.
Handique discloses a thin film resistive heater structure for use in a microfluidic device, wherein the heater is embedded at a lower side of a microchannel and electrically insulated therefrom (figure 1, resistive heater 140 is embedded in glass base 130 beneath oxide layer 150; “lower substrate 125 includes a glass base 130 and an oxide layer 150. Within oxide layer 150, resistive heaters 140 and electric leads 160 are formed”), wherein the heater extends along a directional axis and curves in a serpentine fashion about said axis (as seen in figures 1, 5, 10, 13, 16; note that figure 1 illustrates a conventional heater of the prior art, and figures 5, 10, 13, 16 depict Handique’s inventive heater, and the recited feature in present in both).
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention by using, as the resistive heater of the modified Park device, a resistive heater with a serpentine geometry, based on Handique’s teaching that this is a suitable known shape for a thin film resistive heater in a microfluidic device. The selection of a known component (i.e. a thin film with 2D serpentine shape as known from Handique), based on its suitability for the intended use, is within the ambit of one of ordinary skill in the art [MPEP § 2144.07].
Response to Arguments
Applicant’s arguments, see pg 8-13 of Remarks filed 11 December 2025, with respect to the rejections of claims 1 and 25, have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, new grounds of rejection are made in view of Williams and Handique.
Applicant amends claim 1 to recite a curved heater shape, and claim 25 to recite an insulating coating at least 0.5 µm thick, and argues that these features are not taught in the Park reference.
Examiner agrees, and for these reasons the art rejections of record are withdrawn.
However, resistive heaters with serpentine shapes are known in the art of microfluidic devices as disclosed in Handique, and there is apparent motivation to substitute the induction electrodes of Park with a resistive heating element as taught in Williams to provide for more effective electrothermal vortex generation in portions of the channel with depleted ion concentration. Williams further discloses placing 1.0 µm of electrically insulating coating between the resistive heater and the microchannel. Therefore new 103 grounds are established based on the previously applied references in further view of Williams and Handique.
Applicant’s other arguments are not found persuasive.
Applicant posits that the recitation “extending along an axis and curving about that axis” is a reasonable generalization of the shape illustrated in the figures and described in the specification. Examiner respectfully disagrees – the language “extending along an axis and curving about that axis” encompasses a far broader genus of shapes than the sole species supported by the original disclosure, i.e. a serpentine geometry seen in the figures and stated in instant pg 17. For this reason, the limitation “extending along an axis and curving about that axis” is considered to be noncommensurate in scope with the disclosure and is rejected on 112(a) grounds.
Applicant argues that the word “controllable”, in claims 1 and 25, effectively implies that the claimed device includes a controller configured to perform the recited operation. Examiner respectfully disagrees – the recitation of a heater that can be controlled to perform an operation does not require the claimed device to contain a programmed controller. Case law pertinent to controller-implemented functional limitations can be found at MPEP 2114(IV); in particular note that the court in Intel Corp. v. U.S. Int'l Trade Comm’n, 946 F.2d 821, 832, 20 USPQ2d 1161, 1171 (Fed. Cir. 1991) held that "programmable" claim language requires only that the recited product could be programmed to perform the claimed functionality, not that it is so programmed. By analogy, the recitation that the electrodes are “controllable” does not require the device to actually contain a controller to carry out the recited control operation. Examiner also notes that Applicant’s originally filed disclosure does not contain the words “controller”, “computer”, or “processor”, so there would be a lack of written description if the claim were to require a controller.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/ANDREW KOLTONOW/Examiner, Art Unit 1795
/LUAN V VAN/Supervisory Patent Examiner, Art Unit 1795