Construction of a high-sensitive and high-speed fluorescence lifetime measurement system and its application for tumor diagnosis

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We have tried to construct a novel fluorescence lifetime measurement system with a subpicosecond time resolution by using a photomultiplier-tube internal-gating technique. Finally, we are going to use the measurement system to discriminate a tumor cell from a normal one basing on difference in numerical values of fluorescence lifetimes. A feature of the system is to operating the system so as to work like a boxcar-integrator by employing an asynchronous sampling technique with two mode locked lasers and a nonlinear kerr gate. At present, we have not obtained a stable operation yet because of a lack in the laser power. To solve this problem, we are going to use a regenerative amplifier for the excitation pump laser. On the one hand, however, we have developed 1) a new extrapolation method using an iterative Hilbert-transform procedure that is applicable for band-limited frequency data obtained from a Fourier-transform phase-modulation fluorometer, 2) a deconvolution procedure for determination of fluorescence decay waveform applicable to a band-limited measurement system that has a time delay, and 3) a method for analyzing data obtained from a frequency-multiplexed phase-modulation fluorometer using an autoregressive model. We have obtained some fundamental experimental results by using those methods. We are now going to continue the project to reach the final goal by using the developed techniques.