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 .
Response to Amendment
The amendment filed on June 5, 2026 is acknowledged. Claims 1-5, 7, 8, 11, 15-21, 26-28, 30 and 34 remain pending. Applicant amended* claims 1, 3, 5, 7, 11, 20 and 28.
*Despite claim 16 having underlined language, it was not amended. The underlined language was present in the previous iteration of the claim.
Response to Arguments
The amendment necessitated the new grounds of rejection set forth below, rendering moot Applicant’s arguments.
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.
Claim 20 is rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Despite the amendment and accompanying remarks, claim 20 remains indefinite. Contrary to the implication of Applicant’s remarks (see Remarks 6), the issue is not whether the specification provides support for the subject matter recited in claims 15 and 20. The issue is that the subject matter of claims 15 and 20 is mutually exclusive. It is unclear how cellular particles and non-cellular particles are introduced into a device as a mixture (see claim 15), and at the same time the very particles of claim 15 are introduced into the device separately (see claim 20). Even [0091] of the specification to which Applicant refers (see Remarks 6) discloses that the subject matter of claims 15 and 20 are alternative processes (see “or”). It should be noted that because claim 20 is dependent on claim 15, claim 20 encompasses the subject matter of claim 15. Consequently, claim 20 cannot recite subject matter that is mutually exclusive with the subject matter of claim 15.
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.
Claims 1, 3, 7, 8 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Manalis et al. (“Manalis1”) (US 2010/0288043 A1) in view of Manalis et al. (“Manalis2”) (WO 2018/236708 A1).
With respect to claim 1, Manalis1 discloses a method for optimized cellular measurement, the method comprising the steps of:
introducing a sample comprising cellular material 4 (see abstract and Fig. 1) into a measurement device 1 comprising a sample channel 2, a secondary channel 3 comprising at least one suspended microchannel resonator (SMR) (see [0029]), and a sensor operating over a sensing region (see Fig. 4 illustrating sensor readout);
classifying particles (mass, size or density, see [0004]) in the sample in real-time (see [0014] disclosing measuring change over time) using a classifier (the classification must be performed by a computer/processor) that utilizes data from the sensor; and
controlling flow of the particles from the sample channel into the secondary channel based on output from the classifier (see [0030] disclosing that flow is reversed “when desired”, i.e. after classification).
The method taught by Manalis1 differs from the claimed invention in that Manalis1 does not disclose that the classifier is trained to discriminate between cellular material and non-cellular material. Naturally, the classifier does not classify particles as cellular material or non-cellular material.
Manalis2 discloses a microfluidic device comprising an SMR for classifying particles (see abstract), wherein the device uses a low-pass filter and a high pass filter to screen signals generated by the SMR (see lines 14-30, p. 49). This is done to filter signals produced by non-cellular particles (e.g. debris) detected by the SMR. Id. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have configured the classifier taught by Manalis1, via signal filters, to classify particles as cellular material (cells) or non-cellular material (debris). The modification would improve the accuracy of the measurements and ensure that the device of Manalis1 traps cells instead of debris for analysis. If the modification is made, then the method taught by Manalis1 would comprise a step of classifying particles as cellular material or noncellular material, and controlling flow of particles (e.g. decide whether to retain a particle or reverse flow to purge the particle, see Fig. 1) based on the classification.
With respect to claim 3, the sensor can be a CCD (see [0034] and Fig. 5), which is an imaging sensor comprising an array of pixel elements that captures image data of the sensing region. While the embodiment illustrated in Figure 5 is an alternative embodiment, it is analogous to the device illustrated in Fig. 1 in that it comprises a sample channel (a leg of the U-shaped channel), and a secondary channel (the bridge of the U-shaped channel) comprising at least one SMR (see [0034]). Consequently, reliance on Figure 5 of Manalis1 does not undermine the rejection of claim 1 above.
With respect to claim 7, the method further comprises obtaining a measurement from the SMR for each particle in the secondary channel 3 (see [0028]), and pairing the measurement of each particle with a corresponding measurement (this is evident; otherwise, the device would not be able to process multiple particles).
With respect to claim 8, the cellular material comprises cells (see abstract), and the non-cellular material would be debris (see rejection of claim 1).
With respect to claim 11, as discussed above (see rejection of claim 1), the sample would comprise a mixture of cells and debris, which are discrete non-cellular particles.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Manalis1 in view of Manalis2 as applied to claims 1, 3, 7, 8 and 11 above, and further in view of Kimmerling et al. (“Kimmerling”) (US 2020/0227168 A1).
With respect to claim 2, while Manalis1 discloses that the classifier can use measurement data of cells to determine a stage or progression of cancer (see [0009]), Manalis1 does not disclose that the classifier uses a neural network architecture to make this determination. Nevertheless, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used a neural network to make the determination. The use of a neural network for such purpose is well-known in the art (see abstract and [0005] of Kimmerling), and the modification would enable the classifier to improve the accuracy of its determination in real-time as it gathers more data (i.e. the neural network learns).
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Manalis1 in view of Manalis2 as applied to claims 1, 3, 7, 8 and 11 above, and further in view of Deliwala (US 9,274,202 B2).
With respect to claim 4, Manalis1 does not explicitly disclose that the sensor (e.g. CCD, photodiode) is lens-free.
Deliwala discloses an optics system (e.g. photodiode) that is lens-free. According to Deliwala, the size and manufacturing costs can be reduced by forgoing the use of a lens (see lines 25-30, col. 7). In light of the disclosure of Deliwala, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used a lens-free imaging sensor in the modified Manalis1 device. In addition, according to Applicant’s own disclosure, the use of a lens-free imaging sensor can be implemented in the sensors taught by Manalis1 (e.g. a CCD) and it is known to produce more compact and simpler hardware (see [0040]).
Allowable Subject Matter
Claims 15-19, 21, 26-28, 30 and 34 are allowed. In addition, claim 5 is objected for being dependent on a rejected claim, but it would be allowable if it is rewritten as an independent claim.
The following is a statement of reasons for the indication of allowable subject matter:
As discussed above, the combination of Manalis1 and Manalis2 discloses a method of classifying particles in a sample as cellular material (cells) or non-cellular material (debris). However, the combination does not disclose or suggest:
distinguishing cellular particles from non-cellular particles when the size and/or mass distribution of the particles overlap, as recited in claim 15; or
selecting a ratio of cellular particles and non-cellular particles to be introduced into the secondary channel based on the output of the classifier, as recited in claim 5.
Regarding independent claim 15, based on the disclosure of Manalis1 and Manalis2, and other prior art directed to SMR-based sensors (e.g. Babcock US 2009/0044608 A1), SMR signals provide information regarding the size and mass of particles, and hence SMR-based sensors would not be able to distinguish cellular particles from non-cellular particles if the size and/or mass distribution of the cellular particles and the non-cellular particles overlap. As discussed above (see rejection of claim 1), the classifier of the modified Manalis1 device would have the ability to distinguish cellular particles (cells) from non-cellular particles (e.g. debris), but only if the SMR signals corresponding to the non-cellular particles fall outside a range delimited by lower and upper thresholds corresponding to cellular particles.
Regarding claim 5, the combination of Manalis1 and Manalis2 teaches altering the direction of flow into and out of the secondary channel. Based on their disclosure, there is no motivation to further modify the method of Manalis1 to arrive at the claimed invention (i.e. adjust a ratio of particles introduced into the secondary channel based on the output of the classifier).
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 PAUL S HYUN whose telephone number is (571)272-8559. The examiner can normally be reached M-F 8:30-5:00.
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/PAUL S HYUN/ Primary Examiner, Art Unit 1796
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