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, 6, 8-12, and 16-26 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lieske (Lieske, T., Uhring, W., Dumas, N. et al. Embedded Fluorescence Lifetime Determination for High-Throughput, Low-Photon-Number Applications. J Sign Process Syst 91, 819–831 (2019). https://doi.org/10.1007/s11265-018-1372-9)..
Regarding Claim 1: Lieske discloses a method for detecting single photons from a sample comprising at least one emitter (Abstract), wherein light pulses separated by a pulse period are generated by a light source to trigger the at least one emitter to emit photons (Fig. 1, function generator and laser diode), and wherein the emitted photons are detected by an acquisition system comprising a detector (Fig. 1, SPAD), wherein the acquisition system comprises an active state, in which the acquisition system is able to detect and correctly record photons, an inactive state in which the acquisition system is unable to detect photons and optionally a twilighting state in which the acquisition system is able to detect photons but unable to correctly record the photons, wherein the acquisition system remains in the inactive state or the twilighting state for a dead time after each detection of a photon (Page 4, Section 3 Counting Rates of TCSPC Electronics: “…TCSPC electronics exhibits a dead-time after a photon has been detected.”), wherein a repetition rate of the light pulses is adjusted dependent on the dead time of the acquisition system, and an expected emittance lifetime of the at least one emitter (Page 4, Section 3 Counting Rates of TCSPC Electronics: “The time between the pulses should be at least four times the longest lifetime in the sample”).
Regarding Claim 2: Lieske discloses the method according to claim 1, wherein the adjustment of the repetition rate of the light pulses is further dependent on a number of incident photons on the detector per light pulse (Page 4, Section 3 Counting Rates of TCSPC Electronics: 1% rule).
Regarding Claim 3: Lieske discloses the method according to claim 1, wherein the repetition rate is adjusted such that
- for each light pulse triggering a photon emission, the acquisition system is in the active state with a certain confidence level when emitted photons arrive at the detector, and/or
- arrival of incident photons on the detector after switching of the acquisition system from the inactive state to the active state or from the inactive state to the twilighting state but before the next light pulse can be excluded with a certain confidence level (Page 4, Section 3 Counting Rates of TCSPC Electronics: 1% rule; “The time between the pulses should be at least four times the longest lifetime in the sample.”).
Regarding Claim 4: Lieske discloses the method according to claim 1, wherein the pulse period is adjusted according to a monotonically increasing function of the dead time of the acquisition system and the expected emittance lifetime of the at least one emitter (Page 4, Section 3 Counting Rates of TCSPC Electronics: “The time between the pulses should be at least four times the longest lifetime in the sample”).
Regarding Claim 6: Lieske discloses the method according to claim 1, wherein a photon confidence level is provided, wherein the photon confidence level is a measure for a probability that if one or more photon emissions are triggered by a respective light pulse, no photon emission was triggered after a maximum emittance time after the light pulse previous to the respective light pulse, wherein the repetition rate is adjusted based on the photon confidence level and/or the maximum emittance time (Page 4, Section 3 Counting Rates of TCSPC Electronics: “The time between the pulses should be at least four times the longest lifetime in the sample.”; 1% rule).
Regarding Claim 8: Lieske discloses the method according to claim 6, wherein the pulse period (tp) is adjusted to τmax+τdor more, wherein τmax indicates the maximum emittance time of the at least one emitter and td indicates the dead time of the acquisition system (Page 4, Section 3 Counting Rates of TCSPC Electronics: “The time between the pulses should be at least four times the longest lifetime in the sample.”).
Regarding Claim 9: Lieske the method according to claim 6, wherein the repetition rate is adjusted to different values during a measurement such that the photon confidence level is in a pre-defined range during the measurement (Page 4, Section 3 Counting Rates of TCSPC Electronics: 1% rule).
Regarding Claim 10: Lieske discloses the method according to claim 6, wherein given that the dead time of the acquisition system is equal to or greater than the maximum emittance time, the repetition rate is adjusted such that at least one of the light pulses occurs within the dead time after the previous light pulse, and such that the pulse period equals at least twice the maximum emittance time, or, in case the acquisition system remains in a twilighting state for a twilighting time period at the end of the dead time after each detected photon, the repetition rate is adjusted such that the pulse period equals at least twice the maximum emittance time plus the twilighting time period (Page 4, Section 3 Counting Rates of TCSPC Electronics: “The time between the pulses should be at least four times the longest lifetime in the sample.”).
Regarding Claim 11: Lieske discloses the method according to claim 6, wherein a count rate of the photons detected by the acquisition system is determined, wherein the number of incident photons per light pulse is continuously determined from the current count rate and repetition rate, and wherein the repetition rate is re-adjusted or the photon confidence level is re-determined based on the determined count rate (Page 4, Section 3 Counting Rates of TCSPC Electronics: “The time between the pulses should be at least four times the longest lifetime in the sample.”; 1% rule).
Regarding Claim 12: Lieske discloses the method according to claim 6, wherein a measurement is performed, in which the single photons from the sample are detected, wherein measurement data are generated based on the detected photons during the measurement, and wherein the measurement data are annotated based on the photon confidence level and/or the repetition rate (Fig. 2).
Regarding Claim 16: Lieske discloses the method according to claim 1, wherein one or several measured lifetimes or lifetime distributions of the at least one emitter are determined from the arrival times of the single photons detected by the acquisition system relative to the light pulses, wherein only photon arrivals within a time window after each light pulse are taken into account for said determination and the time window is shorter than the pulse period. (Section 3).
Regarding Claim 17: Lieske discloses a device for detecting single photons from a sample comprising at least one emitter, wherein the device is configured to implement the method according to claim 1 (Fig. 1).
Regarding Claim 18: Lieske discloses a method for detecting single photons from a sample comprising at least one emitter (Abstract), wherein light pulses separated by a pulse period are generated by a light source to trigger the at least one emitter to emit photons (Fig. 1, function generator and laser diode), and wherein the emitted photons are detected by an acquisition system comprising a detector (Fig. 1, SPAD), wherein the acquisition system comprises an active state, in which the acquisition system is able to detect and correctly record photons, an inactive state in which the acquisition system is unable to detect photons and optionally a twilighting state in which the acquisition system is able to detect photons but unable to correctly record the photons, wherein an input comprising a desired value of the repetition rate is received via a user interface, wherein a photon confidence level is determined based on the received input, a dead time of the acquisition system, an expected emittance lifetime of the at least one emitter and a number of incident photons on the detector per light pulse wherein the acquisition system remains in the inactive state or the twilighting state for the dead time after each detection of a photon, and wherein the photon confidence level is a measure for a probability that if one or more photon emissions are triggered by a respective light pulse, no photon emission was triggered after a maximum emittance time after the light pulse previous to the respective light pulse, wherein an output representing said photon confidence level or indicating whether the photon confidence level is outside of a pre-determined range or a record of said photon confidence level is generated.
(Page 4, Section 3 Counting Rates of TCSPC Electronics).
Regarding Claim 19: Lieske discloses a device for detecting single photons from a sample comprising at least one emitter, wherein the device is configured to implement the method according to claim 18 (Fig. 1).
Regarding Claim 20: Lieske discloses a method for detecting single photons from a sample comprising at least one emitter (Abstract), wherein light pulses separated by a pulse period are generated by a light source to trigger the at least one emitter to emit photons (Fig. 1), and wherein the emitted photons are detected by an acquisition system comprising a detector (Fig. 1), wherein the acquisition system comprises an active state, in which the acquisition system is able to detect and correctly record photons, an inactive state in which the acquisition system is unable to detect photons and optionally a twilighting state in which the acquisition system is able to detect photons but unable to correctly record the photons, wherein the acquisition system remains in the inactive state or the twilighting state for a dead time after each detection of a photon, wherein the dead time of the acquisition system is adjusted dependent on a repetition rateof the light pulses, and an expected emittance lifetime of the at least one emitter (Page 4, Section 3 Counting Rates of TCSPC Electronics).
Regarding Claim 21:Lieske discloses the method according to claim 20, wherein the adjustment of the dead time of the acquisition system is further dependent on a number of incident photons on the detector per light pulse (Page 4, Section 3 Counting Rates of TCSPC Electronics).
Regarding Claim 22: Lieske discloses the method according to claim 20, wherein the acquisition system comprises at least one avalanche photodiode, wherein quenching parameters of the avalanche photodiode are adjusted to adjust the dead time (Fig. 1, SPAD).
Regarding Claim 23: Lieske discloses the method according to claim 20, wherein a photon confidence level is provided, wherein the photon confidence level is a measure for a probability that if one or more photon emissions are triggered by a respective light pulse, no photon emission was triggered after a maximum emittance time after the light pulse previous to the respective light pulse, wherein the dead time is adjusted based on the photon confidence level and/or the maximum emittance time (Page 4, Section 3 Counting Rates of TCSPC Electronics).
Regarding Claim 24: Lieske discloses a device for detecting single photons from a sample comprising at least one emitter, wherein the device is configured to implement the method according to claim 20 (Fig. 1).
Regarding Claim 25: Lieske discloses a method for detecting single photons from a sample comprising at least one emitter (Abstract), wherein light pulses separated by a pulse period are generated by a light source to trigger the at least one emitter to emit photons (Fig. 1), and wherein the emitted photons are detected by an acquisition system comprising a detector (Fig.1 ), wherein the acquisition system comprises an active state, in which the acquisition system is able to detect and correctly record photons, an inactive state in which the acquisition system is unable to detect photons and optionally a twilighting state in which the acquisition system is able to detect photons but unable to correctly record the photons, wherein an input comprising a desired value of the dead time is received via a user interface, wherein a photon confidence level is determined based on the received input, a repetition rate of the light pulses, an expected emittance lifetime of the at least one emitter and a number of incident photons on the detector per light pulse, wherein the acquisition system remains in the inactive state or the twilighting state for the dead time after each detection of a photon, and wherein the photon confidence level is a measure for a probability that if one or more photon emissions are triggered by a respective light pulse, no photon emission was triggered after a maximum emittance time after the light pulse previous to the respective light pulse, wherein an output representing said photon confidence level or indicating whether the photon confidence level is outside of a pre-determined range or a record of said photon confidence level is generated (Page 4, Section 3 Counting Rates of TCSPC Electronics).
Regarding Claim 26: Lieske discloses a device for detecting single photons from a sample comprising at least one emitter, wherein the device is configured to implement the method according to claim 25 (Fig. 1).
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) 5 and 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lieske (Lieske, T., Uhring, W., Dumas, N. et al. Embedded Fluorescence Lifetime Determination for High-Throughput, Low-Photon-Number Applications. J Sign Process Syst 91, 819–831 (2019). https://doi.org/10.1007/s11265-018-1372-9).
Regarding Claim 5: Lieske discloses the method according to claim 4, but Lieske fails to explicitly teach wherein the pulse period is set to a value of tp=τd+a∙τL, wherein td indicates the dead time of the acquisition system, a is a scaling parameter which is a positive real number equal to or greater than 1 and tL indicates the expected emittance lifetime of the at least one emitter.
However, the relationship between pulse period, dead time, and emittance lifetime is well-known in the art, as shown by Page 4, Section 3 Counting Rates of TCSPC Electronics. Therefore, it would have been obvious to someone of ordinary skill in the art to set the pulse period based on the dead-time and expected emittance lifetime, especially given that the pulse period will implicitly be made up at least in part by the dead time and emittance lifetime. One would be motivated to do so on the basis of applying known methods to yield predictable results.
Regarding Claim 7: Lieske discloses the method according to claim 6, but Lieske fails to teach wherein the maximum emittance time is determined by the equation τmax=-τLln(-ln(cp)/E), wherein τL indicates the expected emittance lifetime, ln indicates the natural logarithm, cp indicates said photon confidence level and E indicates the expected number of photons per pulse.
However, it would have been obvious to derive the maximum emittance time based on established and known scientific principles (mono-exponential decay, equation 1 in section 1 of Lieske) as the claimed determination of the maximum emittance involves routine mathematical manipulation of known relationships and optimization of a result-effective variable (See MPEP 2143).
Allowable Subject Matter
Claims 13-15 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.
Regarding Claim 13: Lieske discloses the method according to claim 1, but Lieske fails to teach wherein a measured count rate of the single photons detected by the acquisition system is determined, wherein a systematic error introduced by the emission of at least a second photon per light pulse after detecting a first photon is corrected, yielding a corrected count rate.
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 14 and 15 are allowable by virtue of their dependency on claim 13.
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/MIYA DOWNING/Examiner, Art Unit 2884
/DAVID J MAKIYA/Supervisory Patent Examiner, Art Unit 2884