光纖掃瞄式兆赫波近場顯微術

THz Fiber-Scanning Near-Field Microscopy

邱垂珉(Chui-Min Chiu)

指導教授 ： 孫啟光

國立臺灣大學/電機資訊學院/光電工程學研究所/碩士(2009年)

https://doi.org/10.6342/NTU.2009.01314

摘要

近幾年來，兆赫波在生醫方面的相關研究日益受到重視，利用兆赫波來做生物分子的頻譜分析、影像以及感測，則是目前兆赫波科技發展的主要重點。由於兆赫波具有低能量、非游離性輻射以及直接辨認生物分子的能力，這些特性使得兆赫波可以在不需外加染劑的情況下對樣品做非侵入式的生醫影像分析。
在過去的研究中，大多是利用金屬反射鏡來改變兆赫波在空氣中的傳播路徑，由於缺乏可以長距離且低損耗地傳導兆赫波的波導，至今大部分的兆赫波影像都是利用在焦平面上移動樣品來完成影像的掃描，這種移動樣品的成像方式大大限制了兆赫波在生醫影像上的應用。有鑑於此，前年本實驗室發展出一種極低損耗的次波長兆赫波光纖，可以用來長距離的傳導兆赫波並且具有成本低廉、實作容易、低傳輸損耗、低彎曲損耗和高入射耦合效率…等優點。利用此兆赫波光纖，我們成功建立一套全室溫操作的小體積兆赫波光纖掃描影像系統，並且完成大面積的掃描固定不動的生物樣品，同時得到的影像具有高雜訊比與合理解析度。
然而，兆赫波影像的空間解析度受限於其波長，為了突破繞射極限的限制，我們利用通過次波長的金屬孔洞在近場範圍下來實現小於一個波長的空間解析度，此法就類似於光學中的掃描式近場光學顯微術(SNOM)。我們設計了一個由數個週期性溝槽環繞一個次波長圓孔組成的金屬空間濾波器，用以增強穿透效率同時達到次波長的空間解析度，並將之與先前建立的兆赫波光纖掃描影像系統整合，成功的建立了第一個全室溫操作的直立式小體積全兆赫波光纖掃描式近場顯微鏡，並且可輕易的與一般的光學顯微鏡作結合。在未經染色標定的人體乳癌樣品上所作的兆赫波近場顯微影像中，經由與事後染色標定的病理分析作比對，發現兆赫波近場顯微影像對人體乳癌有極高的靈敏度與特異度。希望未來在臨床應用上，能夠幫助醫生確認病患的乳癌是否已經全部切除乾淨，減少二次手術發生。

關鍵字

單模光纖 ； 兆赫波影像 ； 表面電漿波 ； 近場顯微術 ； 乳癌

並列摘要

Within the last several years, terahertz (THz) science and technology has been attracting much attention for various biomedical applications, such as THz spectroscopy, sensing and imaging of biological molecules and tissues, because different bio-molecules have their distinctive absorption spectra in the THz frequency range. In addition, THz radiation is non-ionizing, and the power levels are many orders of magnitude less than the recommended safety guidelines. Therefore, compared with conventional imaging techniques such as X-ray imaging, THz imaging is believed to be a safe and non-invasive technique.
To date, most of the THz imaging systems has been constructed by many metal reflectors fixed on optical tabletop, and thus THz waves could propagate between these mirrors in free space. THz imaging is performed by moving the sample in front of the focused THz beam by means of a computer-controlled two-dimensional translation stage. This imaging system (sample-scanning) may restrict the future development and the practicability into living tissue, because samples are not always movable in most biomedical imaging applications. Moving the objects, especially in the form of powder or liquid or live biological specimens, sometimes will also disturb the sample frequently. A beam scanning THz imaging system is thus extremely needed.
Recently, we proposed an alternative method which was based on our demonstrated low-loss sub-wavelength polyethylene (PE) fiber to construct a fiber-scanning THz imaging system which has advantages of compact size, all room-temperature operation, high SNR, reasonable spatial resolution, and without moving the imaged objects. The demonstrated THz sub-wavelength PE fiber has advantages including: ease of fabrication, low attenuation constant (< 0.01cm-1), low bending loss, and with a high free space coupling efficiency (typically about 50%). THz waves could be long-distance guided along the sub-wavelength fiber to the sample region and THz images would be acquired by directly 2D scanning of the THz fiber output end.
However, the spatial resolution of THz imaging is limited by the wavelength (0.3mm at 1THz). To improve the spatial resolution, a near-field technology is required, similar to the scanning near-field optical microscopy (SNOM). Hence, based on a fiber-scanning THz imaging system with an optimally designed plasmon-resonance bull’s-eye metallic spatial filter, which is consisted of a single sub-wavelength aperture surrounded by the concentric periodic grooves, we report the first ever demonstration of the transmission-illumination mode of an upright-type all-THz fiber-scanning near-field microscope with a compact size operating at room-temperature, which is capable to be integrated with a common optical microscope. Samples can be observed by the optical microscope immediately without moving after fiber scanning for a THz near-field image. By applying this trans-illumination imaging system to the examination of human breast sections, our preliminary results show that this near-field imaging system could clearly and accurately distinguish between breast cancerous tissues from normal tissues in the same section without any pathologic staining. The distribution regions of breast cancer are also in excellent agreement with pathologic diagnosis by using H&E staining.
In the clinical applications, the demonstrated THz near-field imaging system could help to more accurately define the margins of cancer, minimize the size of normal tissues excised in the breast-conserving surgery (BCS), and reduce the need for any additional surgery procedures.

並列關鍵字

Single-Mode Fiber ； THz Imaging ； Surface Plasmon Polaritons ； Near-Field Microscopy ； Breast Cancer

參考文獻

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