用於臨床成像的1200奈米全光纖飛秒雷射光源

Abstract

常見用於倍頻顯微鏡的雷射激發源為摻鉻鎂橄欖石雷射、光參量放大器或是光參量振盪器，是因為這些激發源可提供具有高脈衝能量以及中心波長靠近1200至1300奈米的光學視窗，但是若要將整台包含激發源的倍頻顯微鏡系統整合成一可移動式微型化的倍頻顯微鏡，由於這些激發源需要大型光學桌來使光學系統穩定，抑或是需要沉重的液氮冷卻系統，使得這些激發源皆不適合。 因此，我在本篇論文中透過自相位調製及其他非線性效應，提出一用於可移動式微型化倍頻顯微鏡的全光纖飛秒雷射激發源，並以反饋迴路程式控制光強度穩定度，降低光纖耦合不穩定及震動或移動時造成的影響。利用中心波長位於 1,070 奈米摻鐿光纖雷射以及具有弱負色散的大模場光子晶體光纖，產生一個峰值波長為1200奈米的紅移光譜，並經由超快啁啾反射鏡組將倍頻顯微鏡物鏡後的脈衝寬度壓縮至48.62 飛秒。我利用此激發源量測人體表皮皮膚樣品，有效率地激發表皮中的基底細胞產生三倍頻訊號，以證明此雷射激發源可用於倍頻顯微鏡。此全光纖飛秒雷射激發源具有穩定、微型化、價格低廉的優勢，可在生物分子探測、或臨床應用等領域，作為倍頻顯微術的激發工具。

The common excitation sources used in harmonic generation microscopy include Cr:forsterite lasers, ultrafast optical parametric amplifiers (OPA), or ultrafast optical parametric oscillators (OPO). These sources are chosen because they provide high pulse energy and have a central wavelength near 1200-1300 nanometers, which is within the optical window for biological imaging. However, integrating the entire harmonic generation microscope system, including the excitation source, into a portable compact microscope is challenging. The conventional excitation sources require large optical tables for stability or heavy liquid nitrogen cooling systems, making them unsuitable for portable applications. Therefore, in this thesis, I propose an all-fiber-based femtosecond laser excitation source for portable compact harmonic generation microscopy. By utilizing self-phase modulation and other nonlinear effects, the system achieved stable intensity control through a feedback loop, reducing the impact of fiber coupling instabilities and vibrations during movement. The system utilized a 1070-nanometer ytterbium-doped fiber laser and a large-mode-area photonic crystal fiber with weak negative dispersion to generate a red-shifted spectrum with a peak wavelength of 1200 nanometers. The pulse width after the objective lens of the microscope was compressed to 48.62 femtoseconds by using a pair of doubled chirped mirror compressors. I demonstrated the effectiveness of this excitation source by measuring human epidermal skin samples, efficiently exciting the basal cells to generate third harmonic signals, thus confirming its suitability for harmonic generation microscopy. This all-fiber-based femtosecond laser excitation source offers advantages such as stability, compact, and affordability, making it a promising tool for harmonic generation microscopy in various applications, including biological molecular detection and clinical imaging.