Recently, lifetime imaging has become a subject of intensive research. Lifetime is an important parameter to understand the dynamics of targeted objects and its applications ranges from fluorescence decay of biological objects to relaxation of semiconductor materials and devices. Many methods, such as time-correlated single photon counting (TCSPC) and phase detection in frequency domain, were developed to measure the characteristic lifetime. These methods are now rather matured and widely applied in various studies. However, these methods are only effective for lifetime longer than 100 picoseconds due to the bandwidth limitation of high-speed electronics. For even faster temporal resolution, novel techniques that do not rely on high-speed electronics will be required. In this study, we are integrating an autocorrelator with a galvo-based laser scanning microscope to enable imaging with very high temporal resolution. The principle and technique of pump-probe is implemented through the autocorrelator. In this way, imaging based pump-probe measurements can be realized. Specifically, we have applied the experimental setup so developed in measuring fluorescent dyes and semiconductor devices.

In this thesis, a home made chirp-controlled pump-probe measurement system has been developed and is used to explain possible mechanism of THz radiation enhancement under positive chirped incident pulse. The chirp-controlled pump-probe measurement system with temporal resolution of around 100 femtosecond and chirp parameter tuning from ¡V350 fs2 to +650 fs2 is demonstrated. Meanwhile, using chirp-controlled pump-probe measurement system, ultrafast dynamics of photogenerated carrier in low-temperature growth GaAs in different chirp by is characterized. The relaxation time of low-temperature growth GaAs in positive chirp pump pulse is 461fs and shorter than one, which is 497fs, in negative chirp pump pulse. The result is explained by the Pump-Dump process in negative chirp pump pulse and similar band-filling effect in positive chirp pump pulse.

In this thesis, a home made chirp-controlled pump-probe measurement system has been developed and is used compare the time-resolved photo-reflectance measurements of GaAs:O with different fabricated condition(2.5¡Ñ10^13 ions/cm^2 (500Kev & 800Kev), 4¡Ñ10^13 ions/cm^2 (1200Kev) and 6¡Ñ10^13 ions/cm^2 (500Kev & 800Kev), 1¡Ñ10^14 ions/cm^2 (1200Kev)).The lower-dose sample were annealed at 0,350,400,450,550 and 600¢J,respectively. The higher-dose sample were annealed at 550¢J. The chirp-controlled pump-probe measurement system with temporal resolution of around 100 femtosecond and chirp parameter tuning from ¡V539 fs^2 to +663 fs^2 is demonstrated. Meanwhile, using chirp-controlled pump-probe measurement system, ultrafast dynamics of photogenerated carrier in GaAs:O in different chirp by laser pulse is characterized.

Optical imaging has been developed quickly in the past decades because it has become an important research tool in biology, biochemistry, and biomedical sciences. Coherence domain optical imaging is one of the well developed optical imaging modalities, as it provides high resolution and long penetration depth. In this dissertation, we will report our work on development of molecular contrast in coherence domain optical imaging. In order to image important molecules which are poor fluorophores, we developed a high resolution molecular imaging technique, pump-probe optical coherence microscopy (PPOCM), which does not rely on fluorescent tags. PPOCM is the fusion of Pump-Probe spectroscopy and optical coherence microscopy (OCM). We have demonstrated the prototype system on a fixed human skin sample containing a nodular melanoma. The results indicate that PPOCM can clearly provide strong contrast between the melanotic and amelanotic regions. This technique can be applied to early diagnosis of melanoma and the mapping of tumor margins during excision. It also can be extended to any biological chromophore with a known absorption spectrum and sufficient concentration. In order to differentiate further multiple chromophores, we developed a spectrally resolved two color pump-probe Optical Coherence Microscopy (SRPPOCM). We showed the prototype system on a red hair and a black hair. Our preliminary results show that the SRPPOCM technique could provide a contrast between pheomelanin and eumelanin. This technique could be used potentially as a clinical tool for diagnosing different progression stages of melanoma. This technique could also be applied to differentiate other mixed chromophores. Second harmonic optical coherence tomography (SHOCT) is non-linear high resolution optical molecular imaging modality which is widely used in non-centrosymmetric material. However, depth ambiguity is associated with SHOCT in tissue sample because forward generated second harmonic signal does not correctly report where the second harmonic signal is generated. We studied the feasibility of collecting the backward generated second harmonic signal from nanocrystals through a Second Harmonic Optical Coherence Tomography in Fourier domain. The preliminary result shows that we can collect backward generated second harmonic signal from nanocrystals which indicates that this technique could suppress the depth ambiguity.

<p>Dermatopathologists need more reliable tools for analyzing biopsies of lesions that are potentially melanomas and determining the best treatment plan for the patient. Previously inaccessible, the chemical and physical properties of melanin provide insight into melanoma biochemistry. Two-color, near-infrared pump-probe microscopy of unstained, human pathology slides reveals differences in the type of melanins and the distribution of melanins between melanomas and benign nevi. Because the pump-probe response of melanin is resilient to aging, even for hundreds of millions of years, this tool could prove useful in retrospective studies to correlate melanin characteristics with patient outcome, thus eliminating the pathologist's uncertainty from the development of this classification method.</p><p>Pump-probe spectroscopy of a variety of melanin preparations including melanins with varying amounts of metal ions and toxins, those that have been photo-damaged or chemically oxidized, and melanins with a homogeneous size distribution shows that the pump-probe response is sensitive to these chemical and physical differences, not just melanin type as previously hypothesized. When sampling the response at several pump wavelengths, the specificity of this technique is derived from the absorption spectra of the underlying chromophores. Therefore, hyperspectral pump-probe microscopy of melanin could serve as an indicator of the chemical environment in a variety of biological contexts. For example, the melanin chemistry of macrophages suggests that these cells oxidize, homogenize, and compact melanin granules; whereas melanocytes produce heterogeneous melanins.</p> / Dissertation

<p>In this dissertation, we develop pump probe spectroscopy as a method to differentiate different chemical varieties of melanin, a common biopigment, and exploit these differences to improve the accuracy of melanoma diagnosis. This method gives insight into the chemical makeup and secondary structure of melanins. Pump probe spectroscopy is implemented in a scanning laser microscope as a form of multiphoton imaging, where it is used to image biopsies of human pigmented cutaneous lesions. Melanoma diagnosis is clinically challenging: the accuracy of visual inspection by dermatologists is highly variable and heavily weighted toward false positives. Even the current gold standard of biopsy results in varying diagnoses among pathologists. Using pump probe imaging, significant chemical and morphological changes were found between melanoma and melanocytic nevi, including increased eumelanin content, chemical heterogeneity and general pigmentation. Signal processing methods revealed further differences between melanoma and melanocytic nevi on the cellular scale. Pump probe imaging directly in H&E stained biopsy samples allows integration of this technique with existing histopathology protocols. High resolution imaging found chemical heterogeneity of melanin within pigmented cells. We show that oxyhemoglobin and deoxyhemoglobin may also be differentiated by pump probe imaging. Epi mode imaging of eumelanin, pheomelanin and microvasculature is demonstrated in vivo in human xenograft mouse models of melanoma.</p> / Dissertation

Konstanz, Univ., Diss., 2007.

Zugl.: Göttingen, Univ., Diss., 2009

Freiburg, Univ., Diss., 2001.

University, Diss., 2003--Jena.