DETAILED ACTION
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 21, 23, 24, 26, 27, 30, 32, 34-37 and 39-42 are rejected under 35 U.S.C. 103 as being unpatentable over Ririe (US 20100105029) in view of Wegener (US 20170204371) and Ogg (US 20160305972).
With respect to claims 21 and 41, Ririe discloses a reader (Figure 8:800) configured to receive a microfluidic device (Figure 1:10). Ririe states in paragraph [0041] that the reader includes at least one valve actuator (“the bladder assembly may have additional pneumatic actuators, such as bladders or pneumatically-driven pistons, corresponding to various channels of pouch 10. When activated, these additional pneumatic actuators form pinch valves to pinch off and close the corresponding channels”) to close a valve (Figure 1:16, 36) of the microfluidic device. Furthermore, the reader includes a heater element (Figure 8:886, 888) configured to apply localized heating to a region of the microfluidic device. The reader additionally includes a plunger actuator (Figure 8:869) configured to push/pull the plungers (Figure 1:67-69) of the microfluidic device, as well as a detector (Figure 8:896) configured to provide measurement values that indicate a presence or absence of a target within a sample. Ririe, however, does not expressly state that the plunger actuator is configured to bidirectionally actuate the plunger of the pump. Ririe teaches the plunger is configured to drive a liquid reagent from a pumping chamber of the pump into the microfluidic device, but does not clearly state that air is withdrawn from the microfluidic device into the pumping chamber and then driven from the pumping chamber back into the microfluidic device.
Wegener discloses a microfluidic device comprising a plurality of valves (Figure 2:78, 80, 82, 84, 86) operated by a plurality of corresponding valve actuators. A bidirectional pump (Figure 2:28) having a plunger and a pump actuator is configured as a syringe is used to transfer fluid through the microfluidic device. Wegener shows how the plunger is depressed to drive a liquid reagent from the pump’s pumping chamber into the microfluidic device. See, for example, Figs. 11-18. Wegener further shows how the plunger moves in a reverse direction to withdraw air from the microfluidic device into the pumping chamber. See Fig. 4. The air captured in the pumping chamber may then be ejected and driven into the microfluidic device to cause reagents and fluids to move to a desired location. See Fig. 5 and paragraph [0037].
Ogg discloses a reader (Figure 1:101) configured to receive a microfluidic device (Figure 1:200). The reader includes a plurality of valves (Figure 2:78, 80, 82, 84, 86) operated by a plurality of corresponding valve actuators. For example, Fig. 9 shows a deformable layer 909 that is activated by a pneumatic layer 911 configured to flex the deformable layer to open and close valves. A bidirectional pump (see Figs. 21-28) having a plunger and a pump actuator is configured as a syringe is used to transfer fluid through the microfluidic device. The pump actuator is described in paragraph [0111] as being a linear stepper motor. Ogg shows how the plunger is depressed to drive a liquid reagent from the pump’s pumping chamber into the microfluidic device. See, for example, Fig. 23. Wegener further shows how the plunger moves in a reverse direction to withdraw air from the microfluidic device into the pumping chamber. The air captured in the pumping chamber may then be ejected and driven into the microfluidic device to cause reagents and fluids to move to a desired location. See Fig. 28 and paragraphs [0133]-[0134].
Before the effective filing date of the claimed invention, it would have been obvious to ensure that the Ririe plunger actuator is configured to bidirectionally actuate a plunger of the pump. Wegener and Ogg teach that repeated upward and downward strokes of a plunger-activated pump allow one to continuously pump fluid through a microfluidic system at different speeds over time. By selectively opening and closing valves, fluid is transferred to different processing chambers when reagents and air are pressurized through the operation of the plunger. Wegener and Ogg further show how this can be advantageous over a single-use pump characterized by only a single downward translation of a plunger.
In the alternative, it is noted that the claims are drawn to a reader “configured to receive a microfluidic device”. The microfluidic device and pump are not positively recited and the particulars of the microfluidic device and pump are not required by the claims. Similarly, the bidirectional movement of fluid into and through the microfluidic device (i.e., “drive a liquid reagent from a pumping chamber of the pump into the microfluidic device; withdraw air from the microfluidic device into the pumping chamber; and drive the air from the pumping chamber into the microfluidic device”) is not required by the claim. Instead, only the plunger actuator is positively claimed and reads on any plunger actuator that could potentially bidirectionally actuate a theoretical pump of a theoretical microfluidic device. The Ririe plunger actuator 869 is fully capable of and configured to push/pull the plunger pumps 67-69 in a manner that satisfies the claimed requirements.
With respect to claims 23, 26 and 27, Ririe, Wegener and Ogg disclose the combination as described above. Ririe further teaches that a control element (Figure 8:894) is used to initiate an assay in the microfluidic device and control a function of the microfluidic device. For example, Ririe teaches that the control element regulates valve configuration, heating, pumping and optical monitoring.
With respect to claim 24, Ririe, Wegener and Ogg disclose the combination as described above. Ririe states in paragraph [0037] that the detector comprises fluorescence detection optics.
With respect to claim 30, Ririe, Wegener and Ogg disclose the combination as described above. Ririe teaches that the heater element is configured to conduct PCR, which requires an annealing temperature between 55-65°C.
With respect to claim 32, Ririe, Wegener and Ogg disclose the combination as described above. Although Ririe does not expressly state what force is applied by the valve actuator, it would have been obvious to consider different values, including between 6 to 8 N. Those of ordinary skill would understand that enough force must be applied in order to fully close a valve and/or to ensure that sufficient pumping and flow rate is produced. Those of ordinary skill would also understand that too much force would potentially damage the microfluidic device. Accordingly, it would be obvious to select an optimum value through routine experimentation. See MPEP 2144.05.
With respect to claims 34 and 35, Ririe, Wegener and Ogg disclose the combination as described above. Ririe further states that the microfluidic chip includes an inlet port (Figure 1:12) configured to receive a sample, a first reaction chamber (Figure 1:20) fluidically coupled to the inlet, and a first pump (Figure 6:268a) coupled to the inlet port, wherein the first pump is configured to move fluid from the inlet port to the first reaction chamber and from the first pump to the inlet port. As discussed above, Wegener and Ogg show how the plunger actuators of the reader are configured to operate syringe pumps so as to deliver a sample fluid into and through the pathways of a microfluidic device. As discussed above, Wegener and Ogg teach that the plunger actuators are bidirectionally actuate the syringe pumps. Ririe further teaches that a second pump (Figure 1:67) is fluidically coupled to a mixing chamber (Figure 1:58), a metering channel (Figure 1:38) is fluidically coupled to the first reaction chamber and to the mixing chamber, and one or more second reaction chambers (Figure 1:60, 80) is fluidically coupled to the mixing chamber. Wegener additionally teaches that the first bidirectional pump 28 and pump actuator is operated in cooperation with a second bidirectional pump 30 having a second plunger and second pump actuator.
With respect to claims 36 and 37, Ririe, Wegener and Ogg disclose the combination as described above. Although it is unclear if Ririe teaches the required flow path order of claim 36 or a heated first reaction chamber as required by claim 37, it would have been obvious to rearrange the flow channels, chambers and heaters disclosed by Ririe to produce a variety of configurations. A mere rearrangement of parts that produces a predictable effect is considered to be prima facie obvious. See MPEP 2144.04. Those of ordinary skill would have understood the benefit of sequentially processing a sample under different conditions in first and second reaction chambers, as well as understood that many reactions require an elevated temperature produced by a heater element.
With respect to claim 39, Ririe, Wegener and Ogg disclose the combination as described above. Ririe shows in Figs. 6 and 8 that the first pump is coupled to the plunger actuator, and that the valves 16, 36 are connected to the valve actuator.
With respect to claim 40, Ririe, Wegener and Ogg disclose the combination as described above. Ririe teaches that the detector is configured to detect the reaction product in the one or more second reaction chambers 60, 80.
With respect to claim 42, Ririe, Wegener and Ogg disclose the combination as described above. As previously discussed, Ririe shows a plurality of pumps 67, 68, 69 that are each configured to transfer reagents through the microfluidic device. Wegener additionally teaches that the first bidirectional pump 28 is operated in cooperation with a second bidirectional pump 30 having a second plunger.
Claims 22 and 31 are rejected under 35 U.S.C. 103 as being unpatentable over Ririe (US 20100105029) in view of Wegener (US 20170204371) and Ogg (US 20160305972) as applied to claim 21, and further in view of Besemer (US 6114122).
With respect to claim 22, Ririe, Wegener and Ogg disclose the combination as described above, however do not appear to teach that the reader includes a pin configured to engage an alignment hole of the microfluidic device.
Besemer discloses a reader (Figure 3A:300) configured to receive a cartridge (Figure 1:100). Besemer teaches that the reader includes a plurality of pins (Figure 3A:352, 354) that correspond to alignment holes (Figure 1:116, 118) of the microfluidic device. This is taught in column 4, lines 16-67.
Before the effective filing date of the claimed invention, it would have been obvious to provide the Ririe reader with pins configured to interact with alignment holes disposed on the microfluidic cartridge. Besemer teaches that this is an effective way to ensure that the cartridge is properly aligned when it is inserted in to the reader (“The cartridge also typically includes alignment structures, e.g., alignment pins, bores, and/or an asymmetrical shape to ensure correct insertion and/or alignment of the cartridge in the assembly devices, fluidics stations, and reader devices”).
With respect to claim 31, Ririe, Wegener, Ogg and Besemer disclose the combination as described above. Besemer further states in claim 29 that piezoelectric elements are useful when used in mixing systems to agitate a sample in a microfluidic environment.
Claim 25 is rejected under 35 U.S.C. 103 as being unpatentable over Ririe (US 20100105029) in view of Wegener (US 20170204371) and Ogg (US 20160305972) as applied to claim 21, and further in view of Kayyem (US 20080202927) and Nielsen (US 20130115607).
Ririe, Wegener and Ogg disclose the combination as described above. Ririe further teaches that the microfluidic device includes a cap (Figure 1:90), but does not appear to teach a cap position detection component for detecting cap leaks.
Kayyem discloses a reader (Figure 4E, 4F, 9) configured to receive a microfluidic device. Kayyem teaches in paragraphs [0031], [0320] and [0350] that cap position detection components are provided on the microfluidic devices for detecting cap leaks.
Nielsen discloses a reader (Figure 1:100) configured to receive a microfluidic device. Nielsen teaches in paragraphs [0090] and [0249] that cap position detection components are provided on the microfluidic devices for detecting cap leaks.
Before the effective filing date of the claimed invention, it would have been obvious to provide the Ririe system with means for detecting leaks from the microfluidic device, including leaks originating at the cap. Kayyem and Nielsen are evidence that leak detectors (e.g., pressure sensors) are commonly used to ensure that microfluidic devices are processed properly during automatic detection within a reader module.
Claims 28 and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Ririe (US 20100105029) in view of Wegener (US 20170204371) and Ogg (US 20160305972) as applied to claim 21, and further in view of Johnson (US 9260693).
Ririe, Wegener and Ogg disclose the combination as described above. Ririe further teaches that the reader includes a magnet actuator (Figure 8:850) configured to manipulate beads located within the microfluidic device. Ririe, however, does not state that the magnet actuator rotates a magnet of the microfluidic device.
Johnson discloses a microfluidic device comprising a magnet provided in a mixing chamber or a reaction chamber. Johnson teaches in column 12, line 31 to column 13, line 9 that a magnet actuator is configured to rotate the magnet (“a rotating magnet may be brought close to a chamber containing a conventional magnetic stir bar, causing that stir bar to rotate and stir or mix the suspension in that chamber”).
Before the effective filing date of the claimed invention, it would have been obvious to provide the Ririe reader with a magnet actuator configured to rotate a magnet within the microfluidic device. Johnson teaches that would allow for effective mixing of reagents in a mixing chamber or reaction chamber. Those of ordinary skill would have recognized that Ririe would be interested in noninvasive mixing means to prepare the nucleic acid sample for amplification, and would have understood that the existing Ririe magnet actuator could be adapted for rotational movement with minimal modification.
Response to Arguments
A new ground of rejection is made in view of the combination of Ririe with Wegener and Ogg. The Ogg reference shows the state of the art regarding the use of a pump and pump actuator to bidirectionally manipulate fluid within a microfluidic device. Fig. 28 depicts how the plunger actuator is operated to fill the pumping chamber of the pump with air and then drive air from the pumping chamber to move fluid through the microfluidic device
As to Applicant’s arguments that Ririe is directed to an air-evacuated pouch assembly, it is noted that the particulars of the pouch assembly (i.e., the “microfluidic device”) are not required by the claims because the claims are drawn to “a reader” that is “configured to receive a microfluidic device”. The microfluidic device, pump and other various features of the microfluidic device are not part of the claimed reader and are not positively recited. Although Ririe does describe, in some embodiments, an air-evacuated pouch assembly, the Ririe reader is fully capable of and configured to process a variety of other hypothetical microfluidic devices, including those that do permit air to be driven from a pumping chamber. Furthermore, the Wegener and Ogg references are cited as evidence that plunger actuators configured to manipulate a pump according to the suggested manner described (but not required) by the claims are known in the art and characterized by a predictable and useful operation.
Conclusion
This is a non-final rejection.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATHAN ANDREW BOWERS whose telephone number is (571)272-8613. The examiner can normally be reached M-F 7am-5pm.
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/NATHAN A BOWERS/Primary Examiner, Art Unit 1799
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