Task Specific Project 2

Specific Aim 2中使用的共焦微型探针（Cell-viZio-GI？）提供了水平横截面图像， 到100 μ m的组织穿透深度。该距离不足以评估肿瘤的存在。 粘膜肌层下的浸润和微转移（图3b），这是准确分期所必需的。 癌症的进展。我们已经实现了500 μ m组织穿透的垂直横截面图像 使用新的双轴共焦结构的离体深度（图8b）。这种取向是首选： 病理学评价，因为它揭示了组织微结构的自然生长和增殖。 此外，我们还开发了一个直径为5 mm（内窥镜兼容）的双轴原型， 使用MEMS（微机电系统）镜在水平（xy-）平面中高速扫描。在 为了实现垂直截面，我们需要开发一种轴向（z）扫描仪， 用于体内成像的速度。 MEMS致动器先前已经被开发用于许多应用，包括计算机硬件， 驱动器，82'83航空流体控制系统，84和光纤操纵器。 静电、热或电磁原理。然而，这些方法中的每一种都在以下方面具有局限性： 可以产生的力的大小或者移动扫描头所需的大小和功率 所需的运动范围。气动驱动为轴向位移提供了一种可靠、稳健的方法， 提供了满足体内扫描要求所需的许多特征，包括1）高 功率/力密度，2）大运动位移，3）设计灵活性，以及4）驱动选择多样性 介质致动速度固有地小于基于MEMS的静电、热和静电致动器的致动速度。 电磁方法，但最近的研究表明，气动（空气驱动）执行器可以实现 在5 Hz下轴向运动高达300 um。86该带宽对于双轴共焦显微镜是足够的 以使用785 nm光获得500 μ m穿透深度的垂直横截面图像。

The confocal miniprobe (Cell-viZio-GI¿) used in Specific Aim 2 provides horizontal cross-sectional images up to 100 (im tissue penetration depth. This distance is insufficient to assess for the presence of neoplastic invasion and micrometastases below the muscularis mucosa (Fig 3b), which is needed to accurately stage the progression of cancer. We have achieved vertical cross-sectional images with 500 ^m tissue penetration depth ex vivo using the novel dual axes confocal architecture (Fig 8b). This orientation is preferred :for pathological evaluation because it reveals the natural growth and proliferation of tissue micro-structures. Furthermore, we have developed a 5 mm diameter (endoscope compatible) dual axes prototype that achieves high speed scanning in the horizontal (xy-) plane using a MEMS (micro-electro-mechanical sytems) mirror. In order to achieve vertical cross-sections, we need to develop an axial (z-) scanner that performs with sufficient speed for in vivo imaging. MEMS actuators have been developed previously for a number of applications, including computer hard drives,82'83 aviation fluid control systems,84 and optical fiber manipulators.85 These designs are based on electrostatic, thermal, or electromagnetic principles. Howev.er, each of these approaches have limitation in either the amount of force that can be generated or by the size and power required to move the scanhead over the desired range of motion. Pneumatic actuation offers a reliable, robust approach for axial displacement that provides many of the features needed to meet in the in vivo scanning requirements, including 1) high power/force density, 2) large motion displacement, 3) design flexibility, and 4) variety in choice of driving medium. The actuation speed is inherently less than that for MEMS-based electrostatic, thermal, and electromagnetic approaches, but a recent study has shown that pneumatic (air-driven) actuators can achieve axial motions as large as 300 urn at 5 Hz.86 This bandwidth is sufficient for the dual axes confocal microscope to achieve vertical cross-sectional images of 500 jam penetration depth using 785 nm light.