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 .
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-4, 8, 15-18, and 22 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Patting, M., Reisch, P., Sackrow, M., Dowler, R., Koenig, M., & Wahl, M. (2017). Fluorescence decay data analysis correcting for detector pulse pile-up at very high count rates. arXiv. https://doi.org/10.48550/ARXIV.1711.01137.
Regarding Claim 1: Patting discloses a method, comprising:
collecting, from a sample during a sample event, an emission spectrum that comprises a plurality of emission signals (3 Experimental results; Fig. 2);
based on reception times associated with emission signals of the plurality of emission signals, determining a lifetime estimation for the sample (Fig. 2);
determining, based at least on the lifetime estimation, a pileup factor affecting receiving emissions from the sample (Patting teaches modeling detector pulse pile-up losses during the fluorescence decay fitting process. The fraction of remaining photons is given by e^-nΔt, and the fraction of lost photons is given by (1- e^-nΔt), corresponding to the claimed pile-up factor (see 2 Proposed Correction Method and equations 1-3); and
based on the determined pileup factor, adjusting a number of emission signals measured during the sample event to generate an estimated number of emissions for the sample event (Fig. 1 and Section 2 Proposed Correction Method).
Regarding Claim 2: Patting discloses the method of claim 1, wherein determining the lifetime estimation for the sample comprises fitting the reception times for the emissions signals to a model function (Fig. 1).
Regarding Claim 3: Patting discloses the method of claim 2, wherein the model function comprises a regression function (Page 5: “This model curve is fitted to the data as usual by means of a nonlinear least squares algorithm”).
Regarding Claim 4: Patting discloses the method of claim 3, wherein the regression function comprises a least squares function (Page 5: “This model curve is fitted to the data as usual by means of a nonlinear least squares algorithm”).
Regarding Claim 8: Patting discloses the method of claim 1, wherein the emission spectrum is a first emission spectrum and is collected by a first detector region, wherein the lifetime estimation is a first lifetime estimation, wherein the pileup factor is a first pileup factor associated with the first detector region, and wherein the method further comprises adjusting, based on the first pileup factor, a number of emission signals measured during the sample event by the first detector region (Figs. 1 and 2; Section 2 Proposed Correction Method).
Regarding Claim 15: Patting discloses an apparatus, comprising:
a computing device comprising:
at least one processor (3 Experimental Results); and
memory configured to store computer-executable instructions that, when executed by the at least one processor (3 Experimental Results), cause the apparatus to:
collect, from a sample during a sample event, an emission spectrum that comprises a plurality of emission signals (3 Experimental results; Fig. 2);
based on reception times associated with emission signals of the plurality of emission signals, determine a lifetime estimation for the sample (Fig. 2);
determine, based at least on the lifetime estimation, a pileup factor affecting receiving emissions from the sample (Patting teaches modeling detector pulse pile-up losses during the fluorescence decay fitting process. The fraction of remaining photons is given by e^-nΔt, and the fraction of lost photons is given by (1- e^-nΔt), corresponding to the claimed pile-up factor (see 2 Proposed Correction Method and equations 1-3)); and
based on the determined pileup factor, adjust a number of emission signals measured during the sample event to generate an estimated number of emissions for the sample event (Fig. 1 and Section 2 Proposed Correction Method).
Regarding Claim 16: Patting discloses the apparatus of claim 15, wherein determining the lifetime estimation for the sample comprises fitting the reception times for the emissions signals to a model function (Fig. 2).
Regarding Claim 17: Patting discloses the apparatus of claim 16, wherein the model function comprises a regression function (Page 5: “This model curve is fitted to the data as usual by means of a nonlinear least squares algorithm”).
Regarding Claim 18: Patting discloses the apparatus of claim 17, wherein the regression function comprises a least squares function (Page 5: “This model curve is fitted to the data as usual by means of a nonlinear least squares algorithm”).
Regarding Claim 22: Patting discloses the apparatus of claim 15, wherein the emission spectrum is a first emission spectrum and is collected by a first detector region, wherein the lifetime estimation is a first lifetime estimation, wherein the pileup factor is a first pileup factor associated with the first detector region, and wherein the method further comprises adjusting, based on the first pileup factor, a number of emission signals measured during the sample event by the first detector region (Figs. 1 and 2; Section 2 Proposed Correction Method).
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.
Claim(s) 9-11 and 23-25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Patting in view of Schonle (US 20240280488 A1).
Regarding Claim 9: Patting discloses the method of claim 8, but Patting fails to teach further comprising:
collecting, from a sample during a sample event, an emission spectrum that comprises a plurality of emission signals (3 Experimental results; Fig. 2);
based on reception times associated with emission signals of the plurality of emission signals, determining a lifetime estimation for the sample (Fig. 2);
determining, based at least on the lifetime estimation, a pileup factor affecting receiving emissions from the sample (Patting teaches modeling detector pulse pile-up losses during the fluorescence decay fitting process. The fraction of remaining photons is given by e^-nΔt, and the fraction of lost photons is given by (1- e^-nΔt), corresponding to the claimed pile-up factor (see 2 Proposed Correction Method and equations 1-3); and
based on the determined pileup factor, adjusting a number of emission signals measured during the sample event to generate an estimated number of emissions for the sample event (Fig. 1 and Section 2 Proposed Correction Method).
Patting fails to teach:
collecting a second emission spectrum from the sample during the sample event with a second detector region;
based on reception times associated with emission signals, determining a second lifetime estimation for the sample;
determining, based at least on the second lifetime estimation, a second pileup factor affecting receiving emissions from the sample; and
based on the determined second pileup factor, adjusting a number of emission signals measured during the sample event by the second detector region.
Schonle teaches a TCSPC system with two detectors (Fig. 2, 21a and 21b).
Therefore, it would have been obvious to someone of ordinary skill in the art to have modified Patting to incorporate the teachings of Schonle and provide a second detector and collect data corresponding to the second detector, including determining the pileup factor and correcting the measurements. One would be motivated to make such a modification on the basis of increasing collection efficiency.
Regarding Claim 10: Patting in view of Schonle discloses the method of claim 1, further comprising dividing the plurality of emission signals into a first channel and a second channel, wherein a count of the first channel differs from a corresponding count of the second channel (Schonle: Fig. 2).
Regarding Claim 11: Patting in view of Schonle discloses the method of claim 10, but both fail to explicitly teach wherein the first channel has a count greater than a corresponding count of the second channel.
However, it would have been obvious to someone of ordinary skill in the art to have adjusted the coupling between the two detectors of Schonle by tuning the ratio of the beam splitters (50a and 50b) and selecting a configuration such that the first detector channel has a count greater than the second. One would be motivated to do so as a matter of routine optimization of a known result-effective variable.
Regarding Claim 23: Patting discloses the apparatus of claim 22, wherein the computer-executable instructions, when executed by the at least one processor, further cause the apparatus to:
collect, from a sample during a sample event, an emission spectrum that comprises a plurality of emission signals (3 Experimental results; Fig. 2);
based on reception times associated with emission signals of the plurality of emission signals, determine a lifetime estimation for the sample (Fig. 2);
determine, based at least on the lifetime estimation, a pileup factor affecting receiving emissions from the sample (Patting teaches modeling detector pulse pile-up losses during the fluorescence decay fitting process. The fraction of remaining photons is given by e^-nΔt, and the fraction of lost photons is given by (1- e^-nΔt), corresponding to the claimed pile-up factor (see 2 Proposed Correction Method and equations 1-3)); and
based on the determined pileup factor, adjust a number of emission signals measured during the sample event to generate an estimated number of emissions for the sample event (Fig. 1 and Section 2 Proposed Correction Method).
Patting fails to teach:
collect a second emission spectrum from the sample during the sample event with a second detector region;
based on reception times associated with emission signals, determine a second lifetime estimation for the sample;
determine, based at least on the second lifetime estimation, a second pileup factor affecting receiving emissions from the sample; and
based on the determined second pileup factor, adjust a number of emission signals measured during the sample event by the second detector region.
Schonle teaches a TCSPC system with two detectors (Fig. 2, 21a and 21b).
Therefore, it would have been obvious to someone of ordinary skill in the art to have modified Patting to incorporate the teachings of Schonle and provide a second detector and collect data corresponding to the second detector, including determining the pileup factor and correcting the measurements. One would be motivated to make such a modification on the basis of increasing collection efficiency.
Regarding Claim 24: Patting discloses the apparatus of claim 15, but fails to teach wherein the computer-executable instructions, when executed by the at least one processor, further cause the apparatus to divide the plurality of emission signals into a first channel and a second channel, wherein a count of the first channel differs from a corresponding count of the second channel.
Schonle teaches a TCSPC system with two detectors (Fig. 2, 21a and 21b).
Therefore, it would have been obvious to someone of ordinary skill in the art to have modified Patting to incorporate the teachings of Schonle and provide a second detector and divide the plurality of emission signals into a first channel and a second channel, wherein a count of the first channel differs from a corresponding count of the second channel. One would be motivated to make such a modification on the basis of increasing collection efficiency.
Regarding Claim 25: Patting discloses the apparatus of claim 24, wherein the first channel has a count greater than a corresponding count of the second channel.
However, it would have been obvious to someone of ordinary skill in the art to have adjusted the coupling between the two detectors of Schonle by tuning the ratio of the beam splitters (50a and 50b) and selecting a configuration such that the first detector channel has a count greater than the second. One would be motivated to do so as a matter of routine optimization of a known result-effective variable.
Claim(s) 13, 14, 27, and 28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Patting.
Regarding Claim 13: Patting discloses the method of claim 1, but Patting does not explicitly teach wherein the adjusting is according to:
TPC = MPC/(1-PLF);
wherein TPC comprises the estimated number of emissions for the sample event, MPC comprises the number of emissions signals measured during the sample event, and PLF comprises the pileup factor.
However, Patting teaches a fraction of photons lost due to pileup: (1- e^-nΔt). Once the fraction of photon counts lost due to pileup is determined and the number of emissions measured is known, the actual number (estimated number) of emissions can be calculated by compensating for the known loss. This is a straightforward mathematical operation requiring only routine skill in the art. The relationship between measured counts and actual emitted counts is a direct mathematical relationship when the fraction of lost signals is known.
Regarding Claim 14: Patting discloses the method of claim 1, but Patting fails to teach further comprising classifying the sample based on the estimated number of emission signals for the sample event.
It would have been obvious to someone of ordinary skill in the art to classify the sample based on the estimated number of emission signals because the estimated number of emission signals corresponds to fluorescence characteristics of the sample. Such fluorescence information is conventionally used to characterize samples involving only routine skill in the art.
Regarding Claim 27: Patting discloses the apparatus of claim 15, but Patting fails to explicitly teach wherein the adjusting is according to:
TPC = MPC/(1-PLF);
wherein TPC comprises the estimated number of emissions for the sample event, MPC comprises the number of emissions signals measured during the sample event, and PLF comprises the pileup factor.
However, Patting teaches a fraction of photons lost due to pileup: (1- e^-nΔt). Once the fraction of photon counts lost due to pileup is determined and the number of emissions measured is known, the actual number (estimated number) of emissions can be calculated by compensating for the known loss. This is a straightforward mathematical operation requiring only routine skill in the art. The relationship between measured counts and actual emitted counts is a direct mathematical relationship when the fraction of lost signals is known.
Regarding Claim 28: Patting discloses the apparatus of claim 15 but fails to teach further comprising classifying the sample based on the estimated number of emission signals for the sample event.
It would have been obvious to someone of ordinary skill in the art to classify the sample based on the estimated number of emission signals because the estimated number of emission signals corresponds to fluorescence characteristics of the sample. Such fluorescence information is conventionally used to characterize samples involving only routine skill in the art.
Allowable Subject Matter
Claims 5-7, 12, 19-21, and 26 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:
Regarding Claim 5: Patting discloses the method of claim 1 but fails to teach wherein the pileup factor is determined as a function of the lifetime estimation and an actual lifetime of the sample.
Since the prior art of record fails to teach the details above, nor is there any reason to modify or combine prior art elements outside of Applicant’s disclosure, the claim is deemed patentable over the prior art of record. Claims 6, 7, and 12 are allowable by virtue of their dependency on claim 5.
Regarding Claim 19: Patting discloses the apparatus of claim 15 but fails to teach wherein the pileup factor is determined as a function of the lifetime estimation and an actual lifetime of the sample.
Since the prior art of record fails to teach the details above, nor is there any reason to modify or combine prior art elements outside of Applicant’s disclosure, the claim is deemed patentable over the prior art of record. Claims 20, 21, and 26 are allowable by virtue of their dependency on claim 19.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MIYA DOWNING whose telephone number is (703)756-1840. The examiner can normally be reached Monday - Friday 8:00 AM - 5:00 PM ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, David Makiya can be reached at (571) 272-2273. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MIYA DOWNING/Examiner, Art Unit 2884
/UZMA ALAM/Supervisory Patent Examiner, Art Unit 2884
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