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 .
This is a NON FINAL REJECTION in response to applicant’s claim amendments and arguments filed February 25, 2026. Claims 1, 2, 4, 7, 8, 11-13, 16, and 18-20 are currently amended. Claims 5 and 17 are canceled from consideration. Claims 1-4, 6-16, and 18-20 are pending review in this correspondence.
Response to Amendment
Objection to claims 7 and 8 for various informalities is withdrawn in view of applicant’s amendments to the claims.
Rejection of claims 3, 4, 6, 8, 9, 11, 12, and 15-20 for being indefinite is withdrawn in view of applicant’s amendments to the claims and cancelation of claim 17.
Rejection of claims 1, 2, 10, 13, and 14 as being anticipated by Bahr et al (US 2020/0363336 A1) is withdrawn in view of applicant’s amendments to claims 1 and 13.
Rejection of claim 4 as being unpatentable over Bahr et al (US 2020/0363336 A1) in view of Rothberg et al (US 2016/0370292 A1) in view of applicant’s amendments to claim 1.
Rejection of claim 7 as being unpatentable over Bahr et al (US 2020/0363336 A1) in view of Lakowicz et al (USP 5,504,337) is withdrawn in view of applicant’s amendments to claim 1.
Rejection of claims 11 and 12 as being unpatentable over Bahr et al (US 2020/0363336 A1) in view of Foster et al (US 2020/0268506 A1) is withdrawn in view of applicant’s amendments to claim 1.
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 following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
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, 2, 10, 13, and 14 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jimenez et al (US 2014/0291550 A1).
With respect to claim 1 Jimenez discloses a variable gain detector (flow cytometer system 100, See Para. 0018), comprising: a circuit (gating circuit, See Para. 0040) that varies the gain applied to a detector (gated light sensors, Para.0040 and sensor 118 in Para. 0018) dynamically between at least two values, a higher value and a lower value, based on an intensity of an incoming signal and at least two signal conditioning circuits (analog-to-digital converters, more than one converter for generating data, See Para. 0020) that separately condition the higher value and the lower value.
With respect to claim 2 Jiminez discloses a sampling circuit (sample line 334 and sample channel 344, See Para. 0034) that samples the higher value and the lower value and digitizes these samples to generate a digitized lower value and a digitized higher value (See Para. 0020 for discussion of signals transmitted by sensors 118 may analog or digital, and when such signals are analog, receivers may include analog-to-digital converters for generating digital datal therefrom).
With respect to claim 10 Jiminez discloses a system for manipulating particles, comprising: a microfabricated cell sorting system (See Para. 0018 for cytometer system 100, cell sorting discussed in Para. 0022), which distinguishes target cells from non-target material (See Para. 0019 for discussion of data records that correspond to individual cells that are evaluated), wherein the target cells are distinguished by a laser-induced fluorescent signal (See Para. 0026 for discussion of laser diode 210), and wherein this laser-induced fluorescent signal is detected by the variable gain detector of claim 1 (See Para. 0030 for discussion of light induced by fluorescence being captured by lens 238 and directed to dichroic mirror 240).
With respect to claim 13 Jiminez discloses a method for operating a variable gain detector, comprising:
providing a circuit having variable gain (gating circuit, See Para. 0040); and
applying dynamically a higher value and a lower value, based on an intensity of an incoming signal and providing at least two conditioning circuits, wherein the two conditioning circuits condition the higher values and the lower values separately (analog-to-digital converters, more than one converter for generating data, See Para. 0020).
With respect to claim 14 Jiminez providing a sampling circuit (sample line 334 and sample channel 344, See Para. 0034) that samples the higher value and the lower value and digitizes these samples to generate a digitized lower value and a digitized higher value (See Para. 0020 for discussion of signals transmitted by sensors 118 may analog or digital, and when such signals are analog, receivers may include analog-to-digital converters for generating digital datal therefrom).
Claim Rejections - 35 USC § 103
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 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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 3 is/are rejected under 35 U.S.C. 103 as being unpatentable over Jimenez et al (US 2014/0291550 A1) in view of Berndt et al (US 5,427,920 A).
Refer above for the disclosure of Jiminez.
With respect to claim 3, Jiminez fails to disclose a demultiplexer that separates the digitized higher value and digitized lower value.
Berndt teaches methods and apparatus for detecting biological activities in a specimen such as blood are disclosed (See Abstract and Col. 2, lines 58-64), further wherein Berndt teaches a demultiplexer connected to an output of each photodiode detector (See Col. 3, lines 66-67).
It would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to further include a demultiplexer as taught by Berndt into the detector of Jiminez because Berndt in order to reduce the number of photodetectors utilized by using twice as many of the less expensive light sources (See col. 3, line 63 - col. 4, line 2).
Claim(s) 4, 6, and 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Jimenez et al (US 2014/0291550 A1) in view of Rothberg et al (US 2016/0370292 A1).
Refer above for the disclosure of Jiminez.
With respect to claim 4, jiminez fails to disclose the circuit includes a gain modulator, an ADC, and a signal processing circuit that demultiplexes and then applies a suitable gain to the higher and the lower sample streams, independently. Applicant should note the italicized limitations are directed to the function of the apparatus and/or the manner of operating the apparatus. If the structural limitations of the claim have been disclosed or sufficiently taught by prior art, then the apparatus of the prior art would be deemed capable of the recitation of claim 4. If the structural limitations are met, it would be deemed that the claimed apparatus would not be differentiated from the apparatus of the prior art (see MPEP §2114).
Rothberg teaches a system for analyzing single molecules, wherein an integrated device includes multiple pixels with sample wells configured to receive a sample, which when excited, emits radiation. The system also includes an instrument that interfaces with the integrated device. The instrument may include an excitation energy source for providing excitation energy to the integrated device by coupling to an excitation energy coupling region of the integrated device (See abstract). The integrated electronic circuitry may include drive and read-out circuitry 2-215 coupled to the sensors of the pixel array, and signal processing circuitry. The signal processing circuitry may include analog-to-digital converters 2-217 and one or more field-programmable gate arrays and/or digital signal processors 2-219. The electrical signals may be subsequently processed and/or analyzed. Processing or analyzing of electrical signals may occur on a suitable computing device either located on the instrument 2-104 or off instrument, such as computing device 2-120 shown in FIG. 2-1B (See Paras. 0248-0249). Additionally, techniques for shortening the time duration of an excitation pulse may be used to reduce the excitation energy required to detect luminescent markers and thereby reduce or delay bleaching and other damage to the luminescent markers. Techniques for shortening the time duration of the excitation pulse may be used to reduce the power and/or intensity of the excitation energy after a maximum value or peak of the excitation pulse, allowing the detection of shorter lifetimes. Such techniques may electrically drive the excitation source in order to reduce the excitation power after the peak power. This may suppress a tail of the pulse as shown in FIG. 8-2. An electrical driving signal may be tailored to drive the intensity of the pulse of excitation energy to zero as quickly as possible after the peak pulse. An example of a tailored electrical driving signal combined with gain switching is shown in FIG. 8-2. Such a technique may involve reversing the sign of an electrical driving signal after the peak power is produced. Such a tailored electrical driving signal may produce an optical output shown in FIG. 8-2. The electrical signal may be tailored to quickly reduce the carrier density after the first relaxation oscillation or first oscillation of the optical signal. By reducing the carrier density after the first oscillation, a light pulse of just the first oscillation may be generated. The electrical signal may be configured to generate a short pulse that turns the light signal off quickly by reducing the number of photons emitted after a peak in the signal, such as shown by the plot in FIG. 8-3 showing the optical output of such an electrical signal (See Para. 0441).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the components of integrated electronic circuitry of Rothberg, specifically signal processing circuitry that includes analog-to-digital converters and the gain switching technique of Rothberg, into the system of Jiminez in order to drive the intensity of the pulse of excitation energy to zero as quickly as possible after the peak pulse, thus allowing the detection of shorter lifetimes of the sample (See Para. 0441 of Rothberg). Additionally, the incorporation of these electronic devices allows for processing of or analyzing of electrical signals either on or off the device (See Para. 0248 of Rothberg).
With respect to claim 6 the combination of Jiminez and Rothberg teaches that the at least two signal conditioning circuits apply a first gain to the digitized higher value and a second gain to the digitized lower value (See Para. 0020 of Jiminez for utilization of the analog-to-digital converters for generating digital data).
With respect to claim 16, jiminez fails to disclose providing a gain modulator, an ADC, and a signal processing circuit that demultiplexes and then applies a suitable gain to the higher and the lower sample streams, independently. Applicant should note the italicized limitations are directed to the function of the apparatus and/or the manner of operating the apparatus. If the structural limitations of the claim have been disclosed or sufficiently taught by prior art, then the apparatus of the prior art would be deemed capable of the recitation of claim 4. If the structural limitations are met, it would be deemed that the claimed apparatus would not be differentiated from the apparatus of the prior art (see MPEP §2114).
Rothberg teaches a system for analyzing single molecules, wherein an integrated device includes multiple pixels with sample wells configured to receive a sample, which when excited, emits radiation. The system also includes an instrument that interfaces with the integrated device. The instrument may include an excitation energy source for providing excitation energy to the integrated device by coupling to an excitation energy coupling region of the integrated device (See abstract). The integrated electronic circuitry may include drive and read-out circuitry 2-215 coupled to the sensors of the pixel array, and signal processing circuitry. The signal processing circuitry may include analog-to-digital converters 2-217 and one or more field-programmable gate arrays and/or digital signal processors 2-219. The electrical signals may be subsequently processed and/or analyzed. Processing or analyzing of electrical signals may occur on a suitable computing device either located on the instrument 2-104 or off instrument, such as computing device 2-120 shown in FIG. 2-1B (See Paras. 0248-0249). Additionally, techniques for shortening the time duration of an excitation pulse may be used to reduce the excitation energy required to detect luminescent markers and thereby reduce or delay bleaching and other damage to the luminescent markers. Techniques for shortening the time duration of the excitation pulse may be used to reduce the power and/or intensity of the excitation energy after a maximum value or peak of the excitation pulse, allowing the detection of shorter lifetimes. Such techniques may electrically drive the excitation source in order to reduce the excitation power after the peak power. This may suppress a tail of the pulse as shown in FIG. 8-2. An electrical driving signal may be tailored to drive the intensity of the pulse of excitation energy to zero as quickly as possible after the peak pulse. An example of a tailored electrical driving signal combined with gain switching is shown in FIG. 8-2. Such a technique may involve reversing the sign of an electrical driving signal after the peak power is produced. Such a tailored electrical driving signal may produce an optical output shown in FIG. 8-2. The electrical signal may be tailored to quickly reduce the carrier density after the first relaxation oscillation or first oscillation of the optical signal. By reducing the carrier density after the first oscillation, a light pulse of just the first oscillation may be generated. The electrical signal may be configured to generate a short pulse that turns the light signal off quickly by reducing the number of photons emitted after a peak in the signal, such as shown by the plot in FIG. 8-3 showing the optical output of such an electrical signal (See Para. 0441).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the components of integrated electronic circuitry of Rothberg, specifically signal processing circuitry that includes analog-to-digital converters and the gain switching technique of Rothberg, into the method of Jiminez in order to drive the intensity of the pulse of excitation energy to zero as quickly as possible after the peak pulse, thus allowing the detection of shorter lifetimes of the sample (See Para. 0441 of Rothberg). Additionally, the incorporation of these electronic devices allows for processing of or analyzing of electrical signals either on or off the device (See Para. 0248 of Rothberg).
Claim(s) 7 and 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Jimenez et al (US 2014/01291550 A1) in view of Lakowicz et al (USP 5,504,337).
Refer above for the disclosure of Jiminez.
With respect to claim 7 Jiminez fails to disclose the incorporation of a splitter that divides the higher gain elements, and the lower gain elements, into two different data stream, an upper path and a lower path. Applicant should note the italicized limitations are directed to the function of the apparatus and/or the manner of operating the apparatus. If the structural limitations of the claim have been disclosed or sufficiently taught by prior art, then the apparatus of the prior art would be deemed capable of the recitation of claim 7. If the structural limitations are met, it would be deemed that the claimed apparatus would not be differentiated from the apparatus of the prior art (see MPEP §2114).
Lakowicz teaches a system for identifying individual particles or cells which have been labeled with different fluorochromes, on the basis of the lifetime of their fluorescence (See abstract). Signal-suppression capabilities of a flow cytometer according to the present invention are not limited to autofluorescence with a single-exponential decay. For an autofluorescence showing any kind of kinetics, there exists a specific phase setting of the variable phase shifter that causes the autofluorescence signal to become equal to zero. This principal is applicable also to a combination of autofluorescent light and unrejected scattered radiation. The only condition that must be fulfilled in this case is that the relative contributions of autofluorescence and scatter must remain constant. FIG. 6 shows a further embodiment of the present invention which allows for phase detection without intensity dependence and which involves modifications to the embodiment, as variations thereof, presented in FIG. 2. In particular, in FIG. 6, the split output signal 24a of the power spitter 24 (FIG. 2) is fed via the high pass filter 202 to an additional non-phase shifting power splitter 201 which provides two split output signals 201a and 201b which are routed through respective limiters 215a and 215b after amplification in respective variable gain amplifiers 213 and 214. The modulating signal from the frequency generator 21 and the phase-shifter 22 shown in FIG. 2 is also split by a power splitter 23 in two equal output signals 23a and 23b (See Col. 13, lines 8-30).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the splitter of Lakowicz into the system of Jiminez to allow for phase detection without intensity dependence (See Col. 13, lines 18-21).
With respect to claim 19 Jiminez fails to disclose providing a splitter that divides the higher gain elements, and the lower gain elements, into two different data stream, an upper path and a lower path. Applicant should note the italicized limitations are directed to the function of the apparatus and/or the manner of operating the apparatus. If the structural limitations of the claim have been disclosed or sufficiently taught by prior art, then the apparatus of the prior art would be deemed capable of the recitation of claim 7. If the structural limitations are met, it would be deemed that the claimed apparatus would not be differentiated from the apparatus of the prior art (see MPEP §2114).
Lakowicz teaches a system for identifying individual particles or cells which have been labeled with different fluorochromes, on the basis of the lifetime of their fluorescence (See abstract). Signal-suppression capabilities of a flow cytometer according to the present invention are not limited to autofluorescence with a single-exponential decay. For an autofluorescence showing any kind of kinetics, there exists a specific phase setting of the variable phase shifter that causes the autofluorescence signal to become equal to zero. This principal is applicable also to a combination of autofluorescent light and unrejected scattered radiation. The only condition that must be fulfilled in this case is that the relative contributions of autofluorescence and scatter must remain constant. FIG. 6 shows a further embodiment of the present invention which allows for phase detection without intensity dependence and which involves modifications to the embodiment, as variations thereof, presented in FIG. 2. In particular, in FIG. 6, the split output signal 24a of the power spitter 24 (FIG. 2) is fed via the high pass filter 202 to an additional non-phase shifting power splitter 201 which provides two split output signals 201a and 201b which are routed through respective limiters 215a and 215b after amplification in respective variable gain amplifiers 213 and 214. The modulating signal from the frequency generator 21 and the phase-shifter 22 shown in FIG. 2 is also split by a power splitter 23 in two equal output signals 23a and 23b (See Col. 13, lines 8-30).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the splitter of Lakowicz into the method of Jiminez to allow for phase detection without intensity dependence (See Col. 13, lines 18-21).
Claim(s) 11 and 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Jimenez et al (US 2014/0291550 A1) in view of Foster et al (US 2021/0268506 A1).
With respect to claims 11 and 12 Jiminez fails to disclose that the cell sorting system includes a microfabricated valve that separates the target particle from non-target material (claim 11) or that the valve moves in a plane parallel to a fabrication plane and uses electromagnetic actuation (claim 12).
Foster teaches a microfabricated fluidic MEMS droplet dispensing device 10, wherein the device includes a microfabricated fluidic valve or movable member 110 and a number of microfabricated fluidic channels 120, 122 and 140. The fluidic valve 110 and microfabricated fluidic channels 120, 122 and 140 may be formed in a suitable substrate, such as a silicon substrate, using MEMS lithographic fabrication techniques as described in greater detail below. The fabrication substrate may have a fabrication plane in which the device is formed and in which the movable member 110 moves (See Para. 0054). In use, the fluid sample stream may pass through an interrogation region 170, which may be a laser interrogation region, wherein an excitation laser excites fluorescent tag affixed to a target particle. The fluorescent tag may emit fluorescent radiation as a result of the excitation, and this radiation may be detected by a nearby detector, and thus a target particle or cell may be identified. Upon identification of the target particle or cell, the microfabricated MEMS valve may be actuated, as described below, and the flow directed from the non-sort (waste) channel 145 to the sort channel 122, as illustrated in FIG. 2. The actuation means may be electromagnetic, for example. The analysis of the fluorescent signal, the decision to sort or discard a particle, and the actuation of the valve, may be under the control of a microprocessor or computer (See Para. 0057).
It would have been obvious to one of ordinary skill in the art before ethe effective filing date of the claimed invention to incorporate the electromagnetically actuated valve of Foster into the flow cytometry system of Jiminez in order to effectively sort or discard an analyzed particle (See Paras. 0054 and 0057 of Foster).
Claim Rejections - 35 USC § 112
Claims 8, 9, 15, 18, and 20 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter: The cited prior art of reference fails to disclose, teach, or suggest:
a) that the upper path corresponds to higher amplitude samples and the lower path corresponds to lower amplitude samples (claim 8 – claim 9 depends upon claim 8 and inherits the same status);
b) wherein the method further comprises providing a sampling circuit that samples the higher value and the lower value, and digitizes these samples into higher digitized values and lower digitized values (claim 15);
c) wherein the at least two signal conditioning circuits apply a first gain to the higher digitized values and a second gain to the lower digitized values (claim 18); and
g) wherein the upper path corresponds to the higher amplitude digitized values and the lower path corresponds to the lower digitized values (claim 20).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRITTANY I FISHER whose telephone number is (469)295-9182. The examiner can normally be reached IFP.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Lin can be reached at (571) 272-8902. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BRITTANY I FISHER/Examiner, Art Unit 1796 May 30, 2026
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