The confocal miniprobe (Cell-viZio-GI ) used in Specific Aim 2 provides horizontal cross-sectional images upto 100 (im tissue penetration depth. This distance is insufficient to assess for the presence of neoplasticinvasion and micrometastases below the muscularis mucosa (Fig 3b), which is needed to accurately stage theprogression of cancer. We have achieved vertical cross-sectional images with 500 ^m tissue penetrationdepth ex vivo using the novel dual axes confocal architecture (Fig 8b). This orientation is preferred :forpathological 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 achieveshigh speed scanning in the horizontal (xy-) plane using a MEMS (micro-electro-mechanical sytems) mirror. Inorder to achieve vertical cross-sections, we need to develop an axial (z-) scanner that performs with sufficientspeed for in vivo imaging.MEMS actuators have been developed previously for a number of applications, including computer harddrives,82'83 aviation fluid control systems,84 and optical fiber manipulators.85 These designs are based onelectrostatic, thermal, or electromagnetic principles. Howev.er, each of these approaches have limitation ineither the amount of force that can be generated or by the size and power required to move the scanhead overthe desired range of motion. Pneumatic actuation offers a reliable, robust approach for axial displacement thatprovides many of the features needed to meet in the in vivo scanning requirements, including 1) highpower/force density, 2) large motion displacement, 3) design flexibility, and 4) variety in choice of drivingmedium. The actuation speed is inherently less than that for MEMS-based electrostatic, thermal, andelectromagnetic approaches, but a recent study has shown that pneumatic (air-driven) actuators can achieveaxial motions as large as 300 urn at 5 Hz.86 This bandwidth is sufficient for the dual axes confocal microscopeto achieve vertical cross-sectional images of 500 jam penetration depth using 785 nm light.
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