Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim 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 1-32 are rejected under 35 U.S.C. 103 as being unpatentable over Ichiki et al. (US 20170370922) in view of Stern et al. (US 2015/0258544).
Regarding claim 1, Ichiki discloses a microfluidic chip comprising one or more electrochemical biosensors (fig. 6), each biosensor comprising:
a) a flow layer (201) comprising an analyte capture zone (40 capture part; para 80-89; capture part 40 capture and collect a carrier particle from dispersion liquid of the carier particle that is circulated in flow path 10) comprising a first microfluidic rotary mixer (first circular flow path 10 which includes analyte capture zone 40); and
a detection zone (60 in the second circulation flow path 50) comprising a second microfluidic rotary mixer (circular flow path 50) with a sensing region (60) comprising a working electrode (para 110);
wherein the analyte capture zone (40) is separated from and fluidically connected with the detection zone (60) by a microfluidic channel (capture zone 40 is on a separate microfluidic rotary mixer 10 than detection zone 60 which is on a second microfluidic loop 50; both zones are connected as seen in fig. see fig. 6, valve V9 channel or O3, O4, or O4 structures having microfluidic channels that connect the first rotary mixer to the second rotary mixer); and
one or more valves positioned at the flow flayer and intersecting the analyte capture zone and the detection zone (see fig. 6, showing a plurality of valves to control the flow between the two separate rotary mixers
wherein the first and second microfluidic rotary mixers of the flow layer are each a looped microfluidic channel intersected with at least one, at least two, or at least three valves (see fig. 6 which shows a first rotary mixer 10 and a second rotary mixer 50 which are intersected with at least one valve (V9, O4,O2, O3,).
Ichiki does not provide a control layer having the valves located above or below the flow layer.
Stern teaches a microfluidic device have a flow layer 600 having the microfluidic channels therein and a control layer (actuation layer 620) located below the flow layer that has valves which actuated to control fluid flow within the flow layer (para 83-88). A membrane (610) separates the flow layer from the control layer (para 83-88). It would have been obvious to one having an ordinary skill in the art to modify Ichiki to employ a control layer separate from the flow layer in order to control movement within a microfluidic device without the need of actual valves within the flow path of the microfluidic channels as is taught by Stern (para 83-88) in order to reduce the potential clogging of mechanical valves within a channel which reduces flow volume over time.
Regarding claim 2, the microfluidic chip of claim 1, wherein the one or more valves of the control layer comprise a flexible membrane at intersections with the analyte capture zone, the detection zone, or both (flexible membrane 610 as seen in fig. 6 of Stern is provided to separate the flow channel from the control layer).
Regarding claim 3, the microfluidic chip of claim 1, wherein the one or more valves of the control layer form a rotary pump (para 75) comprising at least three valves configured for sequential operability and intersecting the analyte capture zone and/or the detection zone (See fig. 6 of Ichiki, para 75).
Regarding claim 4, the microfluidic chip of claim 3, wherein the rotary pump is a peristaltic pump (para 75, describes a pump having 3 valves which open and close in order to move a fluid around rotary mixer; fig. 6).
Regarding claim 5, the microfluidic chip of claim 1, comprising an inlet zone (10a, fig. 6) comprising one or more microfluidic channels fluidically connected to the analyte capture zone (rotary mixer 10 has multiple channels arranged around a rectangle path 10).
Regarding claim 6, the microfluidic chip of claim 1, comprising a collection zone (waste reservoir 70) comprising one or more microfluidic channels fluidically connected to the detection zone (60).
Regarding claim 7, the microfluidic chip of claim 1, wherein the control layer comprises one or more microfluidic valves (I1,V1, V2, V3, V4, V5) intersecting any one of microfluidic channels fluidically connecting the inlet zone (10a) to the analyte capture zone (40), the analyte capture zone (40) to the detection zone (60), and the detection zone to the collection zone (70)(valves are provided at each intersection and has control over all the flow paths within the device).
Regarding claim 8, the microfluidic chip of claim 1, wherein the control layer is below the flow layer and the valves are pushed up into the flow layer (see fig. 6 of Stern).
Regarding claim 9, the microfluidic chip of claim 1, wherein the flow layer comprises microfluidic channels having a substantially circular cross-section (see fig. 6).
Regarding claim 10, the microfluidic chip of claim 1, wherein the flow layer comprises microfluidic channels having a substantially angular cross-section such as a square, a rectangular, or a triangular cross section, wherein height to width ratio of the microfluidic channels is between about 1:2 and about 1:15 (para 71-74).
Regarding claim 11, the microfluidic chip of claim 1, wherein the flow layer comprises microfluidic channels having a diameter or a height between about 10 um (.01 mm para 67) and 1000 um, and length between about 5 and 100 mm (para 67,177; fig. 6).
Regarding claim 12, the microfluidic chip of claim 1, wherein the microfluidic rotary mixer comprises a looped microfluidic channel having a geometry selected from the group consisting of a square, a rectangular (fig. 6), and a triangular cross-section.
Regarding claim 13, the microfluidic chip of claim 1, wherein the detection zone comprises a trap region comprising a magnet (carrier particles comprises magnetic beads, para. 80), a gel, or a capture substance (carrier particles, magnetic, gold agarose, plastic beads; para 80).
Regarding claim 14, the microfluidic chip of claim 1, wherein the working electrode of the sensing region is coated with a capture moiety (gold moiety, antibody, antigen, para .112).
Regarding claim 15, the microfluidic chip of claim 1, comprising between two and ten electrochemical biosensors (Stern provides multiple electrochemical biosensors, para 152).
Regarding claim 16, a device comprising the microfluidic chip of claim 1 (this limitation does not further structurally limit the instant claim).
Regarding claim 17, the device of claim 16, comprising a microfluidic controlling module (control part, para 220) and a display means (Stern, para 171).
Regarding claim 18, the device of claim 17, wherein the microfluidic controlling module comprises a solenoid valve array (Stern, para 119).
Regarding claim 19, Ichiki teaches a method of making the microfluidic chip of claim 1 or a device comprising the microfluidic chip comprising:
forming the flow layer and/or the control layer using one or more methods selected from the group consisting of stereolithography, soft lithography, laser machining, micromachining, curing, bonding, three-dimensional printing, molding, micromolding, thermal setting, metal deposition, and coating (Stern teaches soft lithography; para 30). It would have been obvious to one having an ordinary sklii in the art at the time of the invention to modify Ichiki to employ soft lithography techniques to make the microfluidic device as these process of making microfluidics are well known as taught by Stern (para 30, 72).
Regarding claim 20, a method of measuring analyte concentration in a sample comprising applying the sample and an analyte capture element to the flow layer of the microfluidic chip of claim 1 or to a device comprising the microfluidic chip. The modified Ichiki provides a device of claim 1 and the teaching of analyte capture element to the flow layer of the microfluidic chip (para 81).
Regarding claim 21, the method of claim 20, comprising mixing the sample and the analyte capture element in the microfluidic rotary mixer of the analyte capture zone to obtain captured analyte (para 78-81).
Regarding claim 22, the method of claim 20, comprising trapping the captured analyte in a trap region of the detection zone (detection zone 60 analyzes the captured analyte at the detection zone having a “trap region” which is being interpreted as any area within the detection zone where the captured analyte resides for detection.
Regarding claim 23, the method of claim 22, comprising trapping the captured analyte in a trap region of the detection zone and washing with buffer. The carrier particle is, as an example, a particle capable of reacting with a sample substance to be detected. The sample substance is, for example, a biomolecule such as a nucleic acid, a DNA, a RNA, a peptide, a protein, and an extracellular vesicle but does not teach a buffer. In para 163-167, teaches the use of a buffer (transport liquid).
Regarding claim 24, the method of claim 21, comprising flowing the captured analyte over the sensing region to contact the one or more electrodes of the sensing region (flowing the captured analyte over the sensing region to contact the electrodes, para 84, 110).
Regarding claim 25, the method of claim 20, comprising adding a substrate reagent and recording a change in current from the sensing region (para 164-168, second reagent).
Regarding claim 26, the method of claim 20, wherein any one of mixing, trapping, washing, and flowing is accomplished using one or more peristaltic pumps (see claim 4 above).
Regarding claim 27, the method of claim 20, comprising detecting a concentration of the analyte in the sample based on a change in current from the sensing region (para 107-117).
Regarding claim 28. (currently amended) The method of claim 20, wherein the microfluidic chip operates with sample volumes between about 0.5 uL and 500 uL (see Stern para 147).
Regarding claim 29, the method of claim20, wherein the microfluidic chip operates at flow rates between about 0.5 uL/min and 15 uL/min (para 82-84).
Regarding claim 30, the method of claim 20, wherein the valves in the microfluidic chip operate at pressures between about 5 psi and 50 psi (Stern para 82, 119).
Regarding claim 31, the method of claim 20, wherein the microfluidic chip operates at valve closure between about 50% and 95% (para 99-102, the act of closing a valve and opening even from 0-100 encompasses the range taught above while a flow is still moving through the valve).
Regarding claim 32, the method of claim 20, wherein the microfluidic chip comprises between two and ten electrochemical biosensors and is configured to measure the concentration of the same analyte with the biosensors, or the concentrations two to ten different analytes with biosensors (Stern provides multiple electrochemical biosensors, para 152).
Response to Arguments
Applicant's arguments filed 6/11/26 have been fully considered but they are not persuasive. Applicant argues, “There is no reason to modify Ichiki's fluidic device to include an additional layer. Ichiki's fluidic devices include a circulation flow path having two or more circulation flow path valves arranged therein. See Ichiki, para. [0018] and Fig. 6. Using the fluidic devices that incorporate the valves in the circulation flow path in one layer, Ichiki achieved successful transport, capture, and redispersion of magnetic particles within Ichiki's fluidic device. Ichiki states that this demonstrated its devices' applicability "to an analysis method of a sample substance such as fluorescence detection on the magnetic particle and electrochemical detection associated with insolubilization reaction (for example, deposition of silver) in which a soluble substance such as a metal ion is converted into an insoluble substance." Ichiki, Examples 1-3. Ichiki attributes the successful operation of its fluidic devices at least to the flow path valves incorporated in the circulation flow path in the same layer. See Ichiki, paras. [0018]-[0020]. The Office action stated it would have been obvious to one having an ordinary skill in the art to modify Ichiki to employ a control layer separate from the flow layer in order to control movement within a microfluidic device without the need of actual valves within the flow path of the microfluidic channels as is taught by Stern (para 83-88) in order to reduce the potential clogging of mechanical valves within a channel which reduces flow volume over time. Proper motivation to separate the valves from the flow path and place actuating valves in a control layer (actuation layer 620) located below the flow layer (600) (para 83-88). A membrane (610) separates the flow layer from the control layer (para 83-88) and does not allow the ducal action or pin valves to come into contact with a fluid which reduces the potential clogging of mechanical valves within a channel which reduces flow volume over time.
Applicant argues, “As illustrated in Figure 6 of Ichiki and stated repeatedly in Ichiki, the capture part 42 and the detection part 60 are arranged at the same position of the circulation flow path. See Ichiki, paras. [0108], [0117], [0140], [0210], and claim 12. Thus, the capture part 42 and the detection part 60 are in one circulation flow path.” The rejection has been modified based upon the amendment that requires the analyte capture zone is separated from and fluidically connected with the detection zone. The analyte capture zone is now mapped to capture part 40 which is in the first microfluidic rotary mixer 10. The flow layer (201) comprising an analyte capture zone (40 capture part; para 80-89; capture part 40 capture and collect a carrier particle from dispersion liquid of the carrier particle that is circulated in flow path 10) comprising a first microfluidic rotary mixer (first circular flow path 10 which includes analyte capture zone 40); and
a detection zone (60 in the second circulation flow path 50) comprising a second microfluidic rotary mixer (circular flow path 50) with a sensing region (60) comprising a working electrode (para 110);
wherein the analyte capture zone (40) is separated from and fluidically connected with the detection zone (60) by a microfluidic channel (capture zone 40 is on a separate microfluidic rotary mixer 10 than detection zone 60 which is on a second microfluidic loop 50; both zones are connected as seen in fig. see fig. 6, valve V9 channel or O3, O4, or O4 structures having microfluidic channels that connect the first rotary mixer to the second rotary mixer).
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMUEL P SIEFKE whose telephone number is (571)272-1262. The examiner can normally be reached Monday-Friday 8-5.
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/SAMUEL P SIEFKE/Primary Examiner, Art Unit 1758
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