DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 03/25/2026 (RCE 04/27/2026) has been entered.
Claim Objections
Claim 1 is objected to because of the following informalities: Examiner suggests amending “[...] the reservoir chamber is located between the fluid inlet end and the fluid outlet end of the flow channel, and is connected to the fluid inlet end of the flow channel” in L9 to read “[...] the reservoir chamber is located between the fluid inlet end and the fluid outlet end of the flow channel, and the reservoir chamber is connected to the fluid inlet end of the flow channel”.
Claim 7 is objected to because of the following informalities: Examiner suggests amending “[...] 10 min-90 min,10 min-40 min, or 15 min-25 min” in L2 to read “[...] 10 min to 90 min, 10 min to 40 min, or 15 min to 25 min”.
Claim 10 is objected to because of the following informalities: Examiner suggests amending “[...] -500 μm and [...] -500 μm; [...] -100 μm and [...] -100 μm” in L2-3 to read “[...] to 500 μm and [...] to 500 μm; [...] to 100 μm and [...] to 100 μm”.
Claim 11 is objected to because of the following informalities: Examiner suggests amending “[...] -200 microns” in L2 to read “[...] to 200 microns”.
Claim 12 is objected to because of the following informalities: Examiner suggests amending “[...] a flow rate of 0.005 mL/h - 10 mL/h” in L2 to read “[...] a flow rate of 0.005 mL/h to 10 mL/h”.
Claims 11-13 are objected to because of the following informalities: “The method according to claims 8”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 8-13 are rejected under 35U.S.C. 112(b) or 35U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35U.S.C. 112, the applicant), regards as the invention.
Claim 8 is unclear reciting “is-separated from the connecting channel by a membrane”, because it is unclear which element is separated from the connecting channel by a membrane.
Claim 10 is unclear reciting “a width of 5-500 μm and a depth of 5-500 μm; the connecting channel has a width of 3-100 μm and a depth of 3-100 μm” because the unit for ‘5’, ‘5’, ‘3’ and ‘3’ are not specified.
Claim 11 is unclear reciting “a diameter in the range of 5-200 microns” because the unit for ‘5’ is not specified.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim(s) 1-5 and 7 is/are rejected under 35 U.S.C. 102a1/a2 as being anticipated by Solomon (US 2016/0361716).
Regarding claim 1, Solomon teaches:
1. A method of using a microfluidic chip, wherein,
the microfluidic chip comprises:
a capture layer, the capture layer comprises capture flow channels (see Figs. 7B & 16 for example),
the capture flow channels comprise one or more capture units (e.g., fluid trap portion 10), wherein each of the one or more capture units includes a flow channel having a fluid inlet end (i.e., fluid inlet end of 1) and a fluid outlet end (i.e., fluid outlet 6 end), a reservoir chamber (e.g., fluidic trap 3), and a capture channel (e.g., constriction piping 5);
the capture flow channels are provided with one or more inlets and one or more outlets (see Fig. 7B for example);
the reservoir chamber (3) is located between the fluid inlet end and the fluid outlet end of the flow channel, and is connected to the fluid inlet end of the flow channel (see Fig. 1A for example);
the capture channel (5) is connected between the reservoir chamber and the fluid outlet end of the flow channel (see Fig. 1A for example);
wherein the capture channel has a diameter smaller than a diameter of target particles (see i.e., constriction piping for air 5, e.g., with width of 90 μm and length of 500 μm preventing the contents in the fluidic trap from escaping ¶ 0035);
the method comprising:
introducing a liquid (e.g., reagent, media solution) containing the target particles (see i.e., a solution containing cells ¶ 0050+) into the capture flow channels of the microfluidic chip (¶ 0033, 0050+), wherein the target particles are retained within at least one reservoir chamber (i.e., trapped cells ¶ 0051+);
introducing a gas (e.g., air) into the capture flow channels (¶ 0033+), the introduction of the gas is capable of displacing the liquid previously present in the capture flow channels and replacing the liquid with gas (¶ 0050+).
With regard to limitations in claim 1 (e.g., [...] wherein the target particles are retained within at least one reservoir chamber; [...] to displace the liquid in the capture flow channels, thereby forming one or more micro-reaction chambers within the at least one reservoir chamber, wherein each micro-reaction chamber comprises an isolated liquid volume containing at least one of the target particles and is surrounded by the gas), these claim limitations are directed to the results obtainable from the steps of introducing a liquid containing the target particles into the capture flow channels of the microfluidic chip, and introducing a gas into the capture flow channels, and the outcome is dependent on the state of the liquid & the gas in the capture flow channels, and the method steps of Solomon would inherently carry out the claimed results. It is noted that recitations that merely states the result of the limitations in the claim adds nothing to the patentability or substance of the claim. Thus, the reference anticipates the subject matter of the claimed invention.
With regard to limitations in claim 7 (e.g., wherein the time required for introducing the gas is 10 min-90 min, 10 min-40 min, or 15 min-25 min), these claim limitations do not specify active method steps, which do not further delineate the claimed method from that of the prior art.
Regarding claims 2-5, Solomon teaches:
2. The method according to claim 1, wherein the one or more target particles comprise one or more types of particles (¶ 0050+).
3. The method according to claim 2, wherein the particles include cells (¶ 0050+).
4. The method according to claim 1, wherein the gas comprises air (¶ 0033, 0050+).
5. The method according to claim 1, wherein the gas is capable of being entered through different inlets (see Figs. 11A-11B for example).
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim(s) 1-13 & 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yang et al. (CN107012067A published 2017/08/04, see Google Patents translated version, CN107012067A - A kind of high flux pairing captures micro-fluidic chip and its application of unicellular/individual particle) in view of Solomon (US 2016/0361716 A1).
Regarding claim 1, Yang et al. teach:
1. A method of using a microfluidic chip, wherein,
the microfluidic chip comprises:
a capture layer (see annotated Fig. 1 & Claim 1 for example), the capture layer comprises capture flow channels (e.g., two parallel flow channels 10, 11, see annotated Fig. 2 & Claim 1 for example),
the capture flow channels comprise one or more capture units (e.g., capture units 8, 9), wherein each of the one or more capture units includes a flow channel (see e.g., 10, 11 for each of 8, 9 in Figs. 2-3 & Claim 1) having a fluid inlet end and a fluid outlet end (see annotated Fig. 3), a reservoir chamber (e.g., liquid storage chamber 14, 15), and a capture channel (e.g., capture channel 16, 17);
the capture flow channels are provided with one or more inlets (e.g., sample inlets 1, 2) and one or more outlets (e.g., outlets 6, 7);
the reservoir chamber (14) is located between the fluid inlet end and the fluid outlet end of the flow channel, and is connected to the fluid inlet end of the flow channel (see annotated Fig. 3 for example);
the capture channel (16) is connected between the reservoir chamber (14) and the fluid outlet end of the flow channel (see annotated Fig. 3 for example);
wherein the capture channel (16) has a diameter smaller than a diameter of target particles (see i.e., The liquid inlet port of the second channel is the capture channel, the diameter is smaller than the captured single microsphere/single cell, Claim1);
the method comprising:
introducing a liquid (e.g., particle/cell suspension) containing the target particles (see e.g., microspheres/particles/cells throughout the reference) into the capture flow channels of the microfluidic chip (see i.e., Step A, P4/last paragraph– P5/¶ 1; see also Step B, P5/¶ 2), wherein the target particles are retained within at least one reservoir chamber (see i.e., because the capture channel (16) is smaller than the particles/cells, the particles/cells are stuck in front of the capture channel (16), Step A, P4/last paragraph– P5/¶ 1);
introducing an oil phase into the capture flow channels (see i.e., Claim 1) to displace the liquid in the capture flow channels, thereby forming one or more micro-reaction chambers within the at least one reservoir chamber, wherein each micro-reaction chamber comprises an isolated liquid volume containing at least one of the target particles and is capable of being surrounded by the oil phase (see i.e., at this time the solution in the storage chamber is retained, forming a water-in-oil droplet containing single particles/cells, thereby isolating single particles/cells in the reservoir chamber. When the oil phase flows through the entire chip, all single particles/cells are isolated in a single water-in-oil droplet, forming an independent reaction unit, and adjacent droplets are separated by the oil phase, and will not interfere with each other. Step D, P5/¶ 4).
Regarding claim 1, Yang et al. teach filling the isolation channel (12) with air (see i.e., the isolation channel is filled with aqueous solution, oil or air, and the pressure of the syringe pump is controlled, Claim 6). However, Yang et al. do not explicitly teach: introducing a gas into the capture flow channels.
See Solomon above.
It is well known in the art to use different types of fluids in a microfluidic device (as evidenced by Solomon and Yang et al.). Although Yang et al. do not explicitly teach introducing a gas into the capture flow channels, it would have been obvious to one of ordinary skill in the art to substitute the oil phase of Yang et al. (see also Solomon ¶ 0004) with air, as taught by Solomon (¶ 0033+), and with reasonable expectation of success, in order to prevent multiple operations and complex logic based controls to manipulate the droplets, as well as to minimize contamination of downstream traps in the array network (Solomon ¶ 0005). The Supreme Court has articulated a number of exemplary rationales that support a conclusion of obviousness including Rationale E. “Obvious To Try” – Choosing From a Finite Number of Identified, Predictable Solutions, with a Reasonable Expectation of Success. The rationale to support a conclusion that the claim would have been obvious is that “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely that product [was] not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under § 103.” KSR, 550 U.S. at ___, 82 USPQ2d at 1397. If any of these findings cannot be made, then this rationale cannot be used to support a conclusion that the claim would have been obvious to one of ordinary skill in the art (MPEP 2143). The Court in KSR, “[w]hen a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one”, 550 U.S. at ___, 82 USPQ2d at 1396 (emphasis added), or solves a problem which is different from that which the applicant was trying to solve, may also be considered for the purposes of 35 U.S.C. 103. See MPEP 2141.
With regard to limitations in claim 1 (e.g., [...] wherein the target particles are retained within at least one reservoir chamber; [...] to displace the liquid in the capture flow channels, thereby forming one or more micro-reaction chambers within the at least one reservoir chamber, wherein each micro-reaction chamber comprises an isolated liquid volume containing at least one of the target particles and is surrounded by the gas), these claim limitations are directed to the results obtainable from the steps of introducing a liquid containing the target particles into the capture flow channels of the microfluidic chip, and introducing a gas into the capture flow channels, and the outcome is dependent on the state of the liquid & the gas in the capture flow channels, and the method steps of modified Yang et al. would inherently carry out the claimed results.
Annotated Figs. 1-3 of Yang et al. (CN 107012067 A)
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Regarding claims 2-5, 8-13, modified Yang et al. teach:
2. The method according to claim 1, wherein the one or more target particles comprise one or more types of particles (see e.g., microspheres/particles/cells throughout the reference).
3. The method according to claim 2, wherein the particles include cells (see Claim 1 for example).
4. The method according to claim 1, wherein the gas comprises air (see Solomon above).
5. The method according to claim 1, wherein the gas is capable of entering the microfluidic chip through different inlets (i.e., 1, 2, 3).
8. The method according to claim 1, wherein
the microfluidic chip further comprises a control layer; and a slide (see Claim 1 for example); and, the capture layer comprises two parallel sets of the capture flow channels (see e.g., 10, 11 in Claim 1 for example) and a connecting channel (e.g., 13) connected between corresponding reservoir chambers of the two parallel sets of the capture flow channels (see Figs. 2-3 for example),
wherein each capture flow channel (10, 11) comprises a plurality of the capture units (e.g., 8, 9) according to claim 1 connected in series end-to-end, respectively (see Fig. 2 for example);
the flow channel of each capture unit (8, 9) of each set of the capture flow channels comprises a U-shaped tube having a left arm and a right arm (see Claim 1 & annotated Fig. 3 for example), wherein the left arm end of the U-shaped tube of one capture unit is connected to the right arm end of the U-shaped tube of the next capture unit, and the reservoir chamber of each unit, located between the left arm and the right arm of the U-shaped tube (see Claim 1 & Fig. 2-3 for example), is:
(i) connected to the fluid inlet end of the U-shaped tube of the flow channel (see Figs. 2, 3 for example);
(ii) provided with the capture channel according to claim 1 and connected to the fluid outlet end of the U-shaped tube of the flow channel (see Figs. 2, 3 for example); and
(iii) provided with the connecting channel, and the connecting channel has a diameter and the diameter of the connecting channel is smaller than the diameter of the target particle (see Claim 1 for example) that is capable of being retained in the reservoir chamber when present in the liquid according to claim 1 (see i.e., Step A, P4/last paragraph – P5/¶ 1; see also Step B, P5/¶ 2);
each of the two parallel sets of the capture flow channels is provided with a sample inlet (e.g., 1, 2), an inlet capable for a gas (one of 4, 5; see Claim 6 for example), and an outlet (e.g., 6, 7);
the control layer comprises a blocking channel (e.g., 12) positioned below the connecting channel, intersecting the connecting channel (see Claim 1 and Fig. 3 for example); and separated from the connecting channel by a membrane (e.g., 18);
the blocking channel is provided with an inlet (see Claim 6 for example).
9. The method according to claim 8, wherein the dimensions of the two sets of capture flow channels and the shape and size of the capture units therein are the same (see Claim 2 and Fig. 2 for example).
10. The method according to claim 8, wherein the two sets of capture flow channels have a width of 5-500 µm and a depth of 5-500 µm; the connecting channel has a width of 3-100 µm and a depth of 3-100 µm (see Claim 2 for example).
11. The method according to claims 8, wherein the one or more target particles have a diameter in the range of 5-200 microns (P4/¶ 7).
12. The method according to claims 8, wherein the one or more target particles are introduced at a flow rate of 0.005 mL/h - 10 mL/h (P4/¶ 12).
13. The method according to claim 8, wherein the microfluidic chip further comprises a driving pump unit (e.g., drive pumps; isolation pump 34) capable of changing the volume of the reservoir chambers (see claim 7 for example), respectively, comprising connected driving pump control network channels (e.g., 32, 33) and driving pump deformation chambers (e.g., 40, 41; see P11/¶ 4 for example); wherein the driving pump control network channels are further provided with driving pump inlets (e.g., 24, 25); the driving pump deformation chambers are located at the top or bottom of the reservoir chambers, respectively, separated by a membrane (e.g., 42, 44).
With regard to limitations in claim 7 (e.g., wherein the time required for introducing the gas is 10 min-90 min, 10 min-40 min, or 15 min-25 min), these claim limitations do not specify active method steps, which do not further delineate the claimed method from that of the prior art.
Regarding claims 6 & 21, modified Yang et al. do not explicitly teach: 6. The method according to claim 1, wherein the gas is introduced into the microfluidic chip at a gas flow rate of 0.02 L/min to 1.00 L/min, or 0.05 L/min to 0.70 L/min. 21. The method according to claim 6, wherein the gas is introduced into the microfluidic chip at a gas flow rate of 0.04 L/min.
It would have been obvious to one of ordinary skill in the art at the time the invention was made to further modify the method of Yang et al. so that the gas is introduced into the microfluidic chip at a gas flow rate of 0.02 L/min to 1.00 L/min, or 0.05 L/min to 0.70 L/min; or 0.04 L/min, as selecting a flow rate necessary for the purpose of capturing particles would have been obvious (P4/¶ 12, P7/¶ 9-11). The Court in KSR, “[w]hen a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one”, 550 U.S. at ___, 82 USPQ2d at 1396 (emphasis added), or solves a problem which is different from that which the applicant was trying to solve, may also be considered for the purposes of 35 U.S.C. 103. See MPEP 2141.
Response to Arguments
Applicant's arguments filed 03/25/2026 have been fully considered but they are not persuasive.
The amendments have been considered and the 35 USC § 112 rejections have been revised.
In response to the Applicant's argument that “in Solomon, the air plug functions as a transport mechanism to move cells between traps, not as a means to displace liquid in flow channels while retaining liquid containing particles within reservoir chambers to form isolated liquid volumes surrounded by gas”, it has been held that to be entitled to weight in method claims, the recited structure limitations therein must affect the method in a manipulative sense, and not to amount to the mere claiming of a use of a particular structure. In addition, the argued limitations in claim 1 (e.g., [...] wherein the target particles are retained within at least one reservoir chamber; [...] to displace the liquid in the capture flow channels, thereby forming one or more micro-reaction chambers within the at least one reservoir chamber, wherein each micro-reaction chamber comprises an isolated liquid volume containing at least one of the target particles and is surrounded by the gas) are directed to the results obtainable from the steps of introducing a liquid containing the target particles into the capture flow channels of the microfluidic chip, and introducing a gas into the capture flow channels, and the outcome is dependent on the state of the liquid & the gas in the capture flow channels, and the method steps of Solomon/modified Yang et al. would inherently carry out the claimed results. It is noted that recitations that merely states the result of the limitations in the claim adds nothing to the patentability or substance of the claim. Thus, the reference anticipates the subject matter of the claimed invention.
In response to applicant's argument that “One of ordinary skill in the art would not have been motivated to simply substitute Yang's oil with gas based on Solomon's teaching because Solomon does not teach using gas to form isolated micro-reaction chambers”, the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
It is well known in the art to use different types of fluids in a microfluidic device (as evidenced by Solomon and Yang et al.). Although Yang et al. do not explicitly teach introducing a gas into the capture flow channels, it would have been obvious to one of ordinary skill in the art to substitute the oil phase of Yang et al. (see also Solomon ¶ 0004) with air, as taught by Solomon (¶ 0033+), and with reasonable expectation of success, in order to prevent multiple operations and complex logic based controls to manipulate the droplets, as well as to minimize contamination of downstream traps in the array network (Solomon ¶ 0005). The Supreme Court has articulated a number of exemplary rationales that support a conclusion of obviousness including Rationale E. “Obvious To Try” – Choosing From a Finite Number of Identified, Predictable Solutions, with a Reasonable Expectation of Success. The rationale to support a conclusion that the claim would have been obvious is that “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely that product [was] not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under § 103.” KSR, 550 U.S. at ___, 82 USPQ2d at 1397. If any of these findings cannot be made, then this rationale cannot be used to support a conclusion that the claim would have been obvious to one of ordinary skill in the art (MPEP 2143). The Court in KSR, “[w]hen a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one”, 550 U.S. at ___, 82 USPQ2d at 1396 (emphasis added), or solves a problem which is different from that which the applicant was trying to solve, may also be considered for the purposes of 35 U.S.C. 103. See MPEP 2141.
Applicant is encouraged to amend the claims to include additional steps detailing the claimed method.
Applicant is thanked for their thoughtful amendments to the claims.
Response to Arguments
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DEAN KWAK whose telephone number is (571)270-7072. The examiner can normally be reached M-TH, 4:30 am - 2:30 pm EST.
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/DEAN KWAK/Primary Examiner, Art Unit 1798
DEAN KWAK
Primary Examiner
Art Unit 1798
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