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 12/09/2025 has been entered. Claims 1-15, 17, and 19-36 remain pending in the application. Claims 20-36 are withdrawn.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-15, 17, and 19 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
Claim 1 recites the limitations “determining a time delta between a first laser of the two or more lasers and a second laser of the two or more lasers based on a difference between a plurality of first timestamps and a plurality of second timestamps; correlating, based on the time delta, data corresponding to the first sample detected by the first side scatter detection module with data corresponding to the first sample detected by the second side scatter detection module to create a single event data for the first sample”.
In accordance with MPEP 2106, the claims are found to recite statutory subject matter (Step 1: YES) and are analyzed to determine if the claims recite any concepts that equate to an abstract idea, law of nature or natural phenomenon (Step 2A: Prong 1).
In the instant application, the limitations of “determining a time delta between a first laser of the two or more lasers and a second laser of the two or more lasers based on a difference between a plurality of first timestamps and a plurality of second timestamps; correlating, based on the time delta, data corresponding to the first sample detected by the first side scatter detection module with data corresponding to the first sample detected by the second side scatter detection module to create a single event data for the first sample” of claim 1 covers performance of a limitation in the mind, i.e. mental process or mathematical calculation. Other than a non-transitory computer readable medium and processor, if the claim limitations, under its broadest reasonable interpretation, covers performance of the limitations in the mind but for the recitation of generic computer components (e.g. non-transitory computer readable medium and processor), then the claim limitations fall within the “Mental Processes” grouping of abstract ideas (MPEP 2106.05(f)). Accordingly, the claims recite abstract ideas (Step 2A: Prong 1: Yes).
This judicial exception is not integrated into a practical application because the claims do not recite any additional elements that reflects an improvement to technology or applies or uses the judicial exception in some other meaningful way (Step 2A, Prong 2: No). The processor limitations are recited at a high-level of generality (i.e., as generic computer) such that it amounts no more than mere instructions to apply the exception using a generic computer component; wherein a general purpose computer is not a particular machine (MPEP 2106.05(b)). Additionally, the preceding steps and limitations are used for data gathering in the abstract idea; wherein, data gathering to be used in the abstract idea is insignificant extra-solution activity, and not a particular practical application. See MPEP 2106.05(g). Further, the step of “storing the single event data…” is additionally an insignificant extra-solution activity to the judicial exception that generally links the use of the judicial exception to a particular technological environment. See MPEP 2106.05(g) and 2106.05(h). Therefore, the claimed limitations do not integrate the abstract idea into a practical application because it does not impose any meaningful limits on practicing the abstract idea. Thus, the claims are directed to an abstract idea that is not integrated into a practical application (Step 2A, Prong 2: No).
The claims 1-15, 17, and 19 do not include additional elements that are sufficient to amount to significantly more than the judicial exception. Regarding the abstract idea, claim 1 merely recites a non-transitory computer and a processor, wherein the claimed limitations of the computing device amount to no more than mere instructions to apply the exception using a generic computer component; wherein a general purpose computer is not a particular machine (MPEP 2106.05(b)). Claim 1 and dependent claims 2-15, 17, and 19 further recites limitations, however these limitations generally link the judicial exception to a particular field of use (MPEP 2106.05(h)) and are used for data gathering, wherein data gathering to be used in the abstract idea is an insignificant extra-solution activity, and not a practical application (see MPEP 2106.05(g)), which alone or in combination do not amount to significantly more. Claims 4-5, 12, 14, 17, and 19 further includes additional abstract ideas of mental processes or calculations (e.g. standard deviation, mean, determining, identifying, correlating). Additionally, the limitations of claims 1-15, 17, and 19 are well-understood, routine and conventional activities as evidenced by the prior art of Vrane (US 20180156711 A1), Lai et al. (US 20200105376 A1), Houston et al. (US 9632030 B1), Shao et al. (US 20230168178 A1; effectively filed 11/30/2021), Wu et al. (US 20120282600 A1), Takeda et al. (US 20180298324 A1), and Kennington (US 20190369002 A1). See MPEP 2106.05(d). The additional elements of the claims 1-15, 17, and 19 do not comprise an inventive concept when considered individually or as an ordered combination that transforms the claimed judicial exception into a patent-eligible application of the judicial exception. Therefore, the claims do not amount to significantly more than the judicial exception itself (Step 2B: No). The claims are not patent eligible.
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.
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.
Claims 1-3, 5, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Vrane (US 20180156711 A1) in view of Lai et al. (US 20200105376 A1).
Regarding claim 1, Vrane teaches a flow cytometry system (abstract; paragraph [0006]; Figs. 6-7) comprising:
a flow cell (Fig. 6, fluidic system 604 with flow cell; Fig. 7, which is a schematic of fluidic system of 604 of Fig. 6, teaches a flow cell 206);
a fluidic pathway (Fig. 7, element 210) in fluid communication with the flow cell (Fig. 7; paragraph [0078]);
a probe (Fig. 7, sample straw 518) in fluid communication with the fluidic pathway (Fig. 7), wherein the probe is configured to input a plurality of samples and aliquots of a separation gas between successive ones of the plurality of samples into the fluidic pathway (interpreted as a functional limitation of the probe, see MPEP 2114; Fig. 7 and paragraphs [0081],[0219] teach the sample straw 518 is capable of sucking fluids from vessels, therefore is structurally capable of inputting samples and gas between samples as claimed);
two or more lasers (Fig. 6, lasers 612,614) positioned such that an illumination spot of each of the two or more lasers is directly on the flow cell (Fig. 6);
two or more side scatter detection modules (Fig. 6, scatter channels 632,634) in communication with the two or more lasers (Fig. 6);
a processor (Fig. 6 and paragraph [0068] teach a computer with a processor) in communication with the two or more side scatter detection modules (Fig. 6);
and a non-transitory computer readable medium having stored therein instructions that are executable to cause the processor to perform functions when using the flow cytometer system (Fig. 6 and paragraph [0068] teaches storage devices, i.e. memory, to store instructions that are executable by the processor to perform functions for the flow cytometer system), including:
detecting, via a first side scatter detection module of the two or more side scatter detection modules, a first sample of the plurality of samples in the fluidic pathway at a first timestamp (paragraphs [0129]-[0132] and Fig. 10B teach first scatter channel 632 detecting a sample in the flow channel at a first timestamp 1051);
detecting, via a second side scatter detection module of the two or more side scatter detection modules, the first sample of the plurality of samples in the fluidic pathway at a second timestamp after the first timestamp (paragraphs [0129]-[0132] and Fig. 10B teach second scatter channel 634 detecting a sample in the flow channel at a second timestamp 1052); and
determining a time delta between a first laser of the two or more lasers and a second laser of the two or more lasers based on a difference between a plurality of first timestamps and a plurality of second timestamps (Fig. 10B and paragraph [0134] teaches obtaining a time delta, or time difference between a particle passing the first and second scatter channel, i.e. first and second laser, based on the difference between the first and second timestamp; paragraphs [0134]-[0135],[0145] teaches sampling a plurality of signals to generate a plurality of digital signals with respective time stamps, and obtaining a time difference, therefore a time delta from a plurality of first and second time stamps are determined); and
correlating, based on the time delta, data corresponding to the first sample detected by the first side scatter detection module with data corresponding to the first sample detected by the second side scatter detection module to create a single event data for the first sample (Fig. 10B and paragraph [0144] teach collecting and assembling information together in an event data package for each particle, which includes pulse information for each scatter channel and the time difference; therefore, it is implicit that the time difference, i.e. time delta, is used to correlate data of the sample of the first side scatter detection module with the second side detection module to create a single event data since pulse information for each scatter channel and time difference are assembled together, wherein assembling the information together regarding the particle is interpreted as correlating or connecting the information together based on the time difference).
While Vrane teaches flow cytometry (abstract), an event data packet is generated and sent to a host computer (paragraph [0144]), and information can be stored in a storage device (paragraph [0147]), Vrane fails to teach: storing the single event data in a Flow Cytometry Standard (FCS) format.
Lai teaches a system for sorting cell populations including analyzing received flow cytometry data (abstract). Lai teaches particle analyzers may further comprise means for recording the measured data and analyzing the data; wherein the data can be stored in tabular form; and wherein the use of standard file formats, such as an “FCS” file format, for storing data from a particle analyzer facilitates analyzing data using separate programs and/or machines (paragraph [0022]). Lai teaches results of a sample analysis from a flow cytometer may be contained within one or more flow cytometry standard format files, e.g., a FCS (paragraph [0038]); wherein the analysis software may further generate metadata about the sample that indicates things such as acquisition instrument ID, patient ID, acquisition conditions and parameters, etc. (paragraph [0038]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the processor and non-transitory computer readable medium of Vrane to incorporate Vrane’s teachings of generating and sending an event data packet and storing data (paragraphs [0144],[0147]) and Lai’s teachings of storing results from flow cytometers in an FCS file format (paragraphs [0022],[0038]) to provide: storing the single event data in a Flow Cytometry Standard (FCS) format. Doing so would have a reasonable expectation of successfully improving storage and organization of the single event data for facilitating analysis of data as taught by Lai (paragraphs [0022],[0038]).
Regarding claim 2, Vrane further teaches wherein a number of the two or more lasers (Fig. 6, two lasers 612,614) is equal to a number of the two or more side scatter detection modules (Fig. 6, two scatter channels 632,634).
Regarding claim 3, Vrane further teaches wherein the number of the two or more lasers and the number of the two or more side scatter detection modules comprises two, three, four, or five (Fig. 6, two lasers 612,614 and two scatter channels 632,634).
Regarding claim 5, Vrane further teaches: wherein the time delta is determined based on a mean of the difference between the plurality of first timestamps and the plurality of second timestamps (paragraphs [0069],[0145] teaches time difference between time stamps are accumulated to determine an average time delay, i.e. mean of the difference of first and second time stamps).
Regarding claim 19, Vrane fails to explicitly teach wherein correlating data corresponding to the first sample detected by the first side scatter detection module with data corresponding to the first sample detected by the second side scatter detection module comprises: accumulating data from the first side scatter detection module and the second side scatter detection module for a predefined time interval in separate queues for each side scatter detection module; and combining data from the first side scatter detection module and the second side scatter detection module if the first timestamp and the second timestamp are within a threshold time difference.
Vrane teaches a packetizer coupled to the scatter channels that collects and assembles information together into an event data packet regarding a particle flowing in the flow channel past the two laser beams; the data packet including time difference between peak time stamps (paragraph [0144]). Vrane teaches a window extension to allow an acquisition system to associate pulses over a range of laser delays (paragraph [0164]). Vrane teaches periodically sampling pulse signals to generate digital signals with respective time stamps, and a threshold value set upon which enable digital sampling of a pulse, and samples are captured at time stamps separated by the sample period (paragraph [0135]); and the last sample is captured at a time stamp TSN after which the amplitude of the pulse signals drops off below the threshold value TH thereby indicating a completion of a digital capture of the pulse (paragraph [0135]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the non-transitory computer readable medium and the processor to incorporate Vrane’s teachings of collecting and assembling scatter channel data from the laser beams into an event data packet (paragraph [0144]) and a threshold that enables sampling of signals (paragraph [0135]) to provide: wherein correlating data corresponding to the first sample detected by the first side scatter detection module with data corresponding to the first sample detected by the second side scatter detection module comprises: accumulating data from the first side scatter detection module and the second side scatter detection module for a predefined time interval in separate queues for each side scatter detection module; and combining data from the first side scatter detection module and the second side scatter detection module if the first timestamp and the second timestamp are within a threshold time difference. Doing so would have a reasonable expectation of successfully improving proper association and packeting of related sample data during a sample period (Vrane, paragraphs [0135],[0144]).
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Vrane in view of Lai as applied to claim 1 above, and further in view of Houston et al. (US 9632030 B1).
Regarding claim 4, while Vrane teaches time difference between time stamps are accumulated to determine an average time delay (paragraphs [0069],[0145]), Vrane fails to teach: wherein the time delta is determined based on a standard deviation of the difference between the plurality of first timestamps and the plurality of second timestamps.
Houston teaches a method for determining fluorescence lifetime of a fluorescent particle in a flow cytometer (abstract). Houston teaches determining time difference between a point of a scatter waveform and a point on a fluorescence waveform, i.e. time delay (column 6, lines 50-53). Houston teaches table of results includes mean of measured time delays and standard deviation of the time delay measurements (column 12, lines 59-63).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the processor and non-transitory computer readable medium of Vrane to incorporate the teachings of calculating mean and standard deviation of time delay measurements of Houston (column 12, lines 59-63) to provide: wherein the time delta is determined based on a standard deviation of the difference between the plurality of first timestamps and the plurality of second timestamps. Doing so would have a reasonable expectation of successfully utilizing known statistical analysis, i.e. standard deviation, to improving characterization and analysis of the time delta.
Claims 6 and 11-15 are rejected under 35 U.S.C. 103 as being unpatentable over Vrane in view of Lai as applied to claim 1 above, and further in view of Shao et al. (US 20230168178 A1; effectively filed 11/30/2021).
Regarding claim 6, Vrane fails to teach: wherein a fiber optic cable, collecting a scatter light signal from the flow cell illuminated by a given laser of the two of more lasers, connects with a given side scatter detection module of the two or more side scatter detection modules.
Shao teaches a flow cytometer including fiber optic cable for receiving scattered light from an incident laser light that is directed at cells/particles passing through the flow cytometer (abstract). Shao teaches the fiber optic cable is an inherently efficient and accurate filter for the acceptance or rejection of the scattered light (abstract). Shao teaches a fiber optical cable captures forward scattered light to direct to a detector, thus allows for improvements in optics and sensitivity (paragraph [0059]). Shao teaches the fiber optic forward scatter detector channel provides significant improvement in forward scattering sensitivity (paragraph [0105]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the flow cytometry system of Vrane to incorporate the teachings of a flow cytometer including a fiber optic cable of Shao (abstract; paragraphs [0059],[0105]) to provide: wherein a fiber optic cable, collecting a scatter light signal from the flow cell illuminated by a given laser of the two of more lasers, connects with a given side scatter detection module of the two or more side scatter detection modules. Doing so would have a reasonable expectation of successfully improving efficiency and accuracy of filtering of scattered light to thus improve sensitivity of detection of light from the flow cytometer as discussed by Shao (abstract; paragraphs [0059],[0105]).
Regarding claim 11, while Vrane teaches two lasers that have two excitation wavelengths (paragraph [0129]), Vrane fails to explicitly teach: wherein the first laser is configured to illuminate only light having a red wavelength, and wherein the second laser is configured to illuminate only light having a blue wavelength.
Shao teaches a flow cytometer including fiber optic cable for receiving scattered light from an incident laser light that is directed at cells/particles passing through the flow cytometer (abstract). Shao teaches a full spectrum flow cytometer can be variably configured with different numbers of lasers and different numbers of detector modules, such as a red and blue laser (paragraph [0055]). Shao teaches the full spectrum flow cytometer has the power to take highly multiplexed assays, thus giving researchers additional flexibility on how they design experiments for a sample of particles (paragraph [0061]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the first and second lasers of Vrane to incorporate the teachings of a full spectrum flow cytometer with red and blue lasers of Shao (paragraphs [0055],[0061]) to provide: wherein the first laser is configured to illuminate only light having a red wavelength, and wherein the second laser is configured to illuminate only light having a blue wavelength. Doing so would have a reasonable expectation of successfully improving flexibility of designing of experiments for desired samples as discussed by Shao (paragraph [0061]).
Regarding claim 12, modified Vrane fails to teach: wherein the non-transitory computer readable medium causes the processor to further perform functions including: detecting, via a third side scatter detection module of the two or more side scatter detection modules, the first sample of the plurality of samples in the fluidic pathway at a third timestamp after the first timestamp; and determining a second time delta between the first laser of the two or more lasers and a third laser of the two or more lasers based on a difference between a plurality of first timestamps and a plurality of third timestamps.
Shao teaches a flow cytometer including fiber optic cable for receiving scattered light from an incident laser light that is directed at cells/particles passing through the flow cytometer (abstract). Shao teaches a full spectrum flow cytometer can be variably configured with different numbers of lasers and different numbers of detector modules, such as five lasers and five detector modules (paragraph [0055]). Shao teaches the full spectrum flow cytometer has the power to take highly multiplexed assays, thus giving researchers additional flexibility on how they design experiments for a sample of particles (paragraph [0061]). Shao teaches five detector modules, each detector module can capture a plurality of raw digital data for a particular particle/cell as each laser beam of the plurality of lasers strike the same particle, and the plurality of raw digital data is captured at slightly different times, i.e. time delay, as the particle/cell passes by each laser beam in the flow channel (paragraph [0060]); therefore, generating different sets of raw digital data for each laser (paragraph [0060]). Shao teaches spectral data signals are processed and time stamped, packeted together into a data packet corresponding to each cell/particle, and analyzed (paragraph [0050]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the non-transitory computer readable medium and the processor of modified Vrane to incorporate the teachings of a full spectrum flow cytometer with at least three lasers and detector modules and time stamping the data signals of Shao (paragraphs [0050], [0055],[0060]-[0061]) to provide: wherein the non-transitory computer readable medium causes the processor to further perform functions including: detecting, via a third side scatter detection module of the two or more side scatter detection modules, the first sample of the plurality of samples in the fluidic pathway at a third timestamp after the first timestamp; and determining a second time delta between the first laser of the two or more lasers and a third laser of the two or more lasers based on a difference between a plurality of first timestamps and a plurality of third timestamps. Doing so would have a reasonable expectation of successfully improving analysis and characterization of samples and improving flexibility of designing of experiments for desired samples via the use and analysis of data from at least three side scatter detection modules and at least three lasers as discussed by Shao (paragraphs [0055],[0061]).
Regarding claim 13, modified Vrane fails to teach wherein the third laser is configured to illuminate only light having a violet wavelength.
Shao teaches a flow cytometer including fiber optic cable for receiving scattered light from an incident laser light that is directed at cells/particles passing through the flow cytometer (abstract). Shao teaches a full spectrum flow cytometer can be variably configured with different numbers of lasers and different numbers of detector modules, such as a violet laser (paragraph [0055]). Shao teaches the full spectrum flow cytometer has the power to take highly multiplexed assays, thus giving researchers additional flexibility on how they design experiments for a sample of particles (paragraph [0061]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified third laser of modified Vrane to incorporate the teachings of a full spectrum flow cytometer with a violet laser of Shao (paragraphs [0055],[0061]) to provide: wherein the third laser is configured to illuminate only light having a violet wavelength. Doing so would have a reasonable expectation of successfully improving flexibility of designing of experiments for desired samples as discussed by Shao (paragraph [0061]).
Regarding claim 14, modified Vrane fails to teach wherein the non-transitory computer readable medium causes the processor to further perform functions including: detecting, via a fourth side scatter detection module of the two or more side scatter detection modules, the first sample of the plurality of samples in the fluidic pathway at a fourth timestamp after the first timestamp; and determining a third time delta between a first laser of the two or more lasers and a fourth laser of the two or more lasers based on a difference between a plurality of first timestamps and a plurality of fourth timestamps.
Shao teaches a flow cytometer including fiber optic cable for receiving scattered light from an incident laser light that is directed at cells/particles passing through the flow cytometer (abstract). Shao teaches a full spectrum flow cytometer can be variably configured with different numbers of lasers and different numbers of detector modules, such as five lasers and five detector modules (paragraph [0055]). Shao teaches the full spectrum flow cytometer has the power to take highly multiplexed assays, thus giving researchers additional flexibility on how they design experiments for a sample of particles (paragraph [0061]). Shao teaches five detector modules, each detector module can capture a plurality of raw digital data for a particular particle/cell as each laser beam of the plurality of lasers strike the same particle, and the plurality of raw digital data is captured at slightly different times, i.e. time delay, as the particle/cell passes by each laser beam in the flow channel (paragraph [0060]); therefore, generating different sets of raw digital data for each laser (paragraph [0060]). Shao teaches spectral data signals are processed and time stamped, packeted together into a data packet corresponding to each cell/particle, and analyzed (paragraph [0050]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the non-transitory computer readable medium and the processor of modified Vrane to incorporate the teachings of a full spectrum flow cytometer with at least four lasers and detector modules and time stamping the data signals of Shao (paragraphs [0050], [0055],[0060]-[0061]) to provide: wherein the non-transitory computer readable medium causes the processor to further perform functions including: detecting, via a fourth side scatter detection module of the two or more side scatter detection modules, the first sample of the plurality of samples in the fluidic pathway at a fourth timestamp after the first timestamp; and determining a third time delta between a first laser of the two or more lasers and a fourth laser of the two or more lasers based on a difference between a plurality of first timestamps and a plurality of fourth timestamps. Doing so would have a reasonable expectation of successfully improving analysis and characterization of samples and improving flexibility of designing of experiments for desired samples via the use and analysis of data from at least four side scatter detection modules and at least four lasers as discussed by Shao (paragraphs [0055],[0061]).
Regarding claim 15, modified Vrane fails to teach wherein the fourth laser is configured to illuminate only light having a yellow wavelength.
Shao teaches a flow cytometer including fiber optic cable for receiving scattered light from an incident laser light that is directed at cells/particles passing through the flow cytometer (abstract). Shao teaches a full spectrum flow cytometer can be variably configured with different numbers of lasers and different numbers of detector modules, such as Red 640 nm, Yellow-Green 561 nm, Blue 488 nm, Violet 405 nm, and UV 355 nm (paragraph [0055]). Shao teaches the full spectrum flow cytometer has the power to take highly multiplexed assays, thus giving researchers additional flexibility on how they design experiments for a sample of particles (paragraph [0061]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the fourth laser of Vrane to incorporate the teachings of a full spectrum flow cytometer with various laser wavelengths including yellow of Shao (paragraphs [0055],[0061]) to provide: wherein the fourth laser is configured to illuminate only light having a yellow wavelength. Doing so would have a reasonable expectation of successfully improving flexibility of designing of experiments for desired samples as discussed by Shao (paragraph [0061]).
Furthermore, the claimed limitations are obvious because all of the claimed elements were known in the prior art and one skilled in the art could have combined the elements (i.e. a laser configured to illuminate only light having a yellow wavelength) by known methods with no change in their respective functions (i.e. illuminating a sample with a yellow wavelength), and the combinations yielded nothing more than predictable results (i.e. providing a laser configured to illuminate only light having a yellow wavelength would yield nothing more than the obvious and predictable result of improving full spectrum analysis of samples in a flow cytometer with various laser wavelengths to improve flexibility of designing experiments). See MPEP 2143(A).
Claims 7-9 are rejected under 35 U.S.C. 103 as being unpatentable over Vrane in view of Lai as applied to claim 1 above, and further in view of Wu et al. (US 20120282600 A1).
Regarding claim 7, Vrane further teaches the flow cytometry system of claim 1, further comprising: a plurality of optical detectors (Fig. 6 and paragraph [0040], optical detectors SSC, FL1, FL2, FL3, FL4, FL5), a filter (Fig. 6 and paragraph [0040] teaches filters for detectors FL1, FL2, FL3, FL4, FL5), an analog-to-digital converter (Fig. 10C and paragraph [0137], ADC), and a field-programmable gate array (Fig. 10B and paragraph [0143], FPGA).
Vrane fails to teach: the flow cytometry system of claim 1, further comprising: a plurality of photomultiplier detectors, a plurality of photodiode detectors.
Wu teaches a system for analyzing blood samples using light scatter and fluorescence measurements (abstract), wherein the apparatus is suitable for flow cytometry (paragraph [0028]). Wu teaches an embodiment of analysis with enhanced fluorescence information, where both at least one photodiode and at least one photomultiplier tube, are needed to detect light scattered by each blood cell passing through a flow cell (paragraph [0027]); and wherein two or more photodiodes are used to measure axial light loss signals, intermediate angle scatter signals, and low angle scatter (paragraph [0027]), and two or more photomultiplier tubes are used for detecting polarized side scatter signals and depolarized side scatter signals (paragraph [0027]). Wu teaches additional photomultiplier tubes are needed for fluorescent measurements within appropriate wavelength ranges, thus allowing for further analysis of blood cells (paragraph [0027]). Wu teaches the analyzer includes a plurality of detectors to measure various different scattered light and fluorescence light (paragraph [0058]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the detectors of Vrane to incorporate the teachings of an apparatus for flow cytometry including two or more photomultiplier tubes and two or more photodiodes of Wu (paragraphs [0027]-[0028],[0058]) to provide: the flow cytometry system of claim 1, further comprising: a plurality of photomultiplier detectors, a plurality of photodiode detectors. Doing so would have a reasonable expectation of successfully improving light scatter and fluorescence measurements, thus improving further analysis of samples in the flow cytometry system as discussed by Wu (paragraphs [0027],[0058]).
Regarding claim 8, Vrane further teaches wherein the filter comprises one or more of a bandpass filter, a longpass filter, and a dichroic filter (paragraph [0040], “band-pass, or long-pass, filters”).
Regarding claim 9, while Vrane teaches at least 12 different optical detectors (Fig. 6 teaches two sets of optical detectors SSC, FL1, FL2, FL3, FL4, FL5), modified Vrane fails to teach wherein the plurality of photomultiplier detectors and the plurality of photodiode detectors comprises one of (i) eight photomultiplier detectors and three photodiode detectors, (ii) sixteen photomultiplier detectors and 4 photodiode detectors, or (iii) twenty-two photomultiplier detectors and five photodiode detectors.
Wu teaches a system for analyzing blood samples using light scatter and fluorescence measurements (abstract), wherein the apparatus is suitable for flow cytometry (paragraph [0028]). Wu teaches an embodiment of analysis with enhanced fluorescence information, where both at least one photodiode and at least one photomultiplier tube, are needed to detect light scattered by each blood cell passing through a flow cell (paragraph [0027]); and wherein two or more photodiodes are used to measure axial light loss signals, intermediate angle scatter signals, and low angle scatter (paragraph [0027]), and two or more photomultiplier tubes are used for detecting polarized side scatter signals and depolarized side scatter signals (paragraph [0027]). Wu teaches additional photomultiplier tubes are needed for fluorescent measurements within appropriate wavelength ranges, thus allowing for further analysis of blood cells (paragraph [0027]). Wu teaches the analyzer includes a plurality of detectors to measure various different scattered light and fluorescence light (paragraph [0058]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the plurality of photomultiplier detectors and the plurality of photodiode detectors of modified Vrane to incorporate the teachings of 12 different optical detectors of Vrane (Fig. 6) and the teachings of two or more photodiodes and two or more photomultiplier tubes of Wu (paragraphs [0027],[0028],[0058]) to provide: wherein the plurality of photomultiplier detectors and the plurality of photodiode detectors comprises one of (i) eight photomultiplier detectors and three photodiode detectors, (ii) sixteen photomultiplier detectors and 4 photodiode detectors, or (iii) twenty-two photomultiplier detectors and five photodiode detectors. Doing so would have been obvious through routine experimentation (MPEP 2144.05(II)) to optimize the number of photomultiplier detectors for detecting necessary side scatter signals and fluorescence measurements within appropriate wavelengths ranges as taught by Wu (paragraph [0027]) and desired by Vrane (Fig. 6) and to optimize the number of photodiode detectors to measure appropriate angled light scattered signals as taught by Wu (paragraph [0027]), and would have a reasonable expectation of successfully improving light scatter and fluorescence measurements, and improving further analysis of samples in the flow cytometry system as discussed by Wu (paragraphs [0027],[0058]).
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Vrane in view of Lai as applied to claim 1 above, and further in view of Takeda et al. (US 20180298324 A1).
Regarding claim 10, Vrane fails to teach wherein the time delta ranges from about 50 μs to about 200 μs between any two adjacent lasers of the two or more lasers.
Takeda teaches an apparatus for analyzing and separating particles in a flow path (abstract). Takeda teaches a flow channel (Fig. 5A, element 22) having two optical signals from two laser illuminations (35, 36). Takeda teaches where the interval ΔL between the illumination positions of the two lasers is 100 μm and the flow rate V is 1 m/sec, the time difference is 100 μsec, and thus the resolution of 0.2 μsec is sufficient (Fig. 5A, paragraph [0145]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the time delta of Vrane to incorporate the teachings of two lasers having a time difference of 100 μs of Takeda (Fig. 5A; paragraph [0145]) to provide: wherein the time delta ranges from about 50 μs to about 200 μs between any two adjacent lasers of the two or more lasers. Doing so would have a reasonable expectation of successfully providing a sufficient analysis resolution as discussed by Takeda (paragraph [0145]).
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Vrane in view of Lai as applied to claim 1 above, and further in view of Kennington (US 20190369002 A1).
Regarding claim 17, Vrane fails to teach wherein the non-transitory computer readable medium causes the processor to further perform functions including: determining, based on one or more properties of the fluid in the fluidic pathway, a presence of a separation gas in the fluid in the fluidic pathway; generating separation gas timing data comprising the detected one or more properties of the fluid in the fluidic pathway and a corresponding timestamp; and identifying a respective sample well of a plurality of sample wells, based, at least in part, on the separation gas timing data.
Kennington teaches a flow cytometer apparatus including a flow cell, fluidic pathway, probe, sensor, processor, and non-transitory computer readable medium (abstract). Kennington teaches high-throughput flow cytometry system use a pump to fill a sample tubing line with a stream of discrete sample particle suspensions aspirated from wells of a microplate and separated one from the other by air bubble gap, which allows individual particle suspensions of individual sample wells to be distinguished and separately evaluated when plotted in conjunction with the time parameter (paragraph [0002]). Kennington teaches the flow cytometer apparatus 200 includes a processor 218 in communication with the sensor 216, and a non-transitory computer readable medium 220 having stored therein instructions that are executable to cause the processor 218 to perform functions including determining, based on the detected one or more properties of the fluid in the fluidic pathway 208, a presence of a separation gas in the fluid in the fluidic pathway 208 (paragraph [0073]). Kennington teaches the non-transitory computer readable medium 220 causes the processor 218 to further perform functions including (i) generating separation gas timing data comprising the detected one or more properties of the fluid in the fluidic pathway 208 and a corresponding timestamp, and (ii) identifying a respective sample well of the plurality of sample wells 228, based, at least in part, on the separation gas timing data (paragraph [0085]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the non-transitory computer readable medium and the processor of Vrane to incorporate the teachings of a high-throughput flow cytometer system with a processor and non-transitory computer readable medium to determine a presence of a separation gas to identify respective sample wells based on timing data of Kennington (abstract; paragraphs [0073],[0085]) to provide: wherein the non-transitory computer readable medium causes the processor to further perform functions including: determining, based on one or more properties of the fluid in the fluidic pathway, a presence of a separation gas in the fluid in the fluidic pathway; generating separation gas timing data comprising the detected one or more properties of the fluid in the fluidic pathway and a corresponding timestamp; and identifying a respective sample well of a plurality of sample wells, based, at least in part, on the separation gas timing data. Doing so would have a reasonable expectation of successfully improving throughput of sampling and analyzing various different wells and allowing individual particle suspensions of individual sample wells to be distinguished and separately evaluated when plotted in conjunction with the time parameter.
Response to Arguments
Applicant’s arguments, see pages 13-14, filed 12/09/2025, with respect to specification objection have been fully considered and are persuasive. The specification objection of 10/10/2025 has been withdrawn.
Applicant's arguments, see pages 14-16, filed 12/09/2025, with respect to the rejections under 35 U.S.C. 101, have been fully considered but they are not persuasive.
In response to applicant’s argument that Claim 1 is subject matter eligible at Step 2A Prong 2 at least because it provides improvements in the technical field of flow cytometry and because the judicial exception is applied in a meaningful way such that the claim as a whole is more than a drafting effort designed to monopolize the exception (Remarks, page 15), the examiner agrees that the specification does describe improvement of flow variations by measuring the time deltas between laser spot locations. However, the specification, paragraph [0067] does not discuss “accurately correlate data”. Additionally, the examiner disagrees that the improvement is reflected in the claims.
MPEP 2106.05(a) states that if it is asserted that the invention improves upon conventional functioning of a computer, or upon conventional technology or technological processes, a technical explanation as to how to implement the invention should be present in the specification; and the claim must be evaluated to ensure the claim itself reflects the disclosed improvement in technology (Intellectual Ventures I LLC v. Symantec Corp., 838 F.3d 1307, 1316, 120 USPQ2d 1353, 1359 (Fed. Cir. 2016)). MPEP 2106.04(d)(1) states if the specification sets forth an improvement in technology, the claim must be evaluated to ensure that the claim itself reflects the disclosed improvement; that is, the claim includes the components or steps of the invention that provide the improvement described in the specification.
For example, the specification, paragraph [0067] discusses “adaptively measure the time deltas between the laser spot locations to enable automatic adaptation to fluidic flow variations” and “initial time delta calibration…to correlate sample data across the multiple laser spot locations”; paragraph [0060] discusses particular wavelengths of the lasers; paragraph [0068] discusses time data calculation used to synchronize events from lasers; and paragraphs [0077]-[0081] discusses specific data processing steps. The claims do not recite the additional elements from the specification as discussed above and therefore the claims do not appear to reflect all of the elements that lead to the improvement in the technology.
In response to applicant’s argument that the limitation of “determining…” is meaningfully limited so as to be integrated into a practical application and the claim as a whole is more than a drafting effort designed to monopolize the alleged exception (Remarks, pages 15-16), the examiner disagrees. The preceding steps and limitations are used for data gathering in the abstract idea; wherein, data gathering to be used in the abstract idea is insignificant extra-solution activity, and not a particular practical application. See MPEP 2106.05(g). Further, the step of “storing the single event data…” is additionally an insignificant extra-solution activity to the judicial exception that generally links the use of the judicial exception to a particular technological environment. See MPEP 2106.05(g) and 2106.05(h). Additionally, the limitations of the claims are well-understood, routine and conventional activities as evidenced by the prior art of Vrane (US 20180156711 A1), Lai et al. (US 20200105376 A1), Houston et al. (US 9632030 B1), Shao et al. (US 20230168178 A1; effectively filed 11/30/2021), Wu et al. (US 20120282600 A1), Takeda et al. (US 20180298324 A1), and Kennington (US 20190369002 A1). See MPEP 2106.05(d). Additionally, the use of a computer or other machinery as claimed in its ordinary capacity for tasks (e.g., to receive, store, or transmit data) or simply adding a general purpose computer or computer components after the fact to an abstract idea (e.g., mathematical equation) does not integrate a judicial exception into a practical application or provide significantly more (MPEP 2106.05(f)). Therefore, the claims are not patent eligible.
Applicant’s arguments, see pages 16-17, filed 12/09/2025, with respect to the rejection(s) of claims 1-3, 5, 16, and 18 under 35 U.S.C. 102, specifically in regards to the amended claim 1 (i.e. storing the single event data in a FCS format), have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Vrane (US 20180156711 A1) in view of Lai et al. (US 20200105376 A1).
In response to applicant’s argument that Vrane fails to teach “correlating, based on the time delta, data corresponding to the first sample detected by the first side scatter detection module with data corresponding to the first sample detected by the second side scatter detection module to create a single event data for the first sample” (Remarks, pages 16-17), the examiner disagrees. Fig. 10B and paragraph [0144] teach collecting and assembling information together in an event data package for each particle, which includes pulse information for each scatter channel and the time difference between peak time stamps. Therefore, the time difference i.e. time delta, is used to correlate data of the sample of the first side scatter detection module with the second side detection module to create a single event data since pulse information for each scatter channel and time difference, i.e. time delta, are assembled together, wherein assembling the information together regarding the particle is interpreted as correlating or connecting the information together based on the time difference. I.e. the data from each side scatter detection module are correlated (i.e. associated, connected, or matched up) based on the time difference since they are collected and assembled together into an event data packet regarding the particle.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Srienc et al. (US 20080268469 A1) teaches a system for analyzing particulates in a flow (abstract), the system adapted for cytometry (paragraph [0054]). Srienc teaches data can be stored and file size can be reduced by storing the data in binary format using a standardized file format as implemented with traditional FCS flow cytometry data files (paragraph [0165]).
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 HENRY H NGUYEN whose telephone number is (571)272-2338. The examiner can normally be reached M-F 7:30A-5:00P.
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/HENRY H NGUYEN/Primary Examiner, Art Unit 1758