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Micro-instrumentation for Colon Cancer Molecular Imaging

Sponsor: NIH National Cancer Institute

According to the national statistics, risk factors of cancer are high for human digestive tract organs. In particular, colon cancer is the 2nd largest cause of death in the U.S. The mission of our research is to develop novel optical imaging technologies for the early detection of colon cancer. The conventional endoscopic method based on white light imaging often fails to detect the early onset of the disease on a flat tissue surface. Crypts in the colon experience morphological changes during the development of tumors. To precisely capture the onset of cancer, we need to obtain the cross-sectional image of crypts with molecular-level selectivity between the normal tissue and the premalignant tissue.

We take a confocal microscopy imaging technique for our medical imaging. The left figure shows a conventional single axis configuration, where a high NA objective lens is used to achieve sub-cellular resolution, and the focal point is scanned using a scanning mirror. But it limits the size of the field of view, preventing us from obtaining the pathologically important cross-sectional view of tissue. Instead, we use a novel dual axes architecture that uses separate, low NA objectives to achieve both sub-cellular resolution and long working distance.  Post-objective scanning provides a large field-of-view and instrument scalability to millimeter dimensions.  With this architecture, we aim to obtain a vertical (V) cross-sectional image while reducing the collection of light scattered by tissue (dashed orange lines).

We use MEMS technology to construct the micro confocal endoscope for in vivo optical imaging. A MEMS micro mirror scanner is used for the post-objective scanning of the illumination and emission lights in the horizontal direction. In order to achieve the vertical scanning, we use a novel z-axis microactuator consisting of multiple metal-PZT film stacks. Prof. Kenn Oldham’s group is leading our effort to develop this z-axis microactuator and integrate it into the endoscope packaging. As a result of our instrumentation research, we expect that we can enable optical biopsy of colon tissue eliminating the need for physically removing a tissue sample form a patient.


Our medical school colleagues (Prof. Tom Wang’s group) are currently working on identifying molecular probes used for the optical imaging. These probes are called peptides, which are fragments of protein molecules. They are expressed by bacteria called M13 phage. A library of M13 phages provides 1012 peptide species with known amino acid sequences. Our colleagues are selecting peptides which can preferentially bind to precancerous tissue surfaces as molecular probes using a technique called biopanning.

References:

Tung, Y.-C., and Kurabayashi, K., “A Metal-Coated Polymer Micromirror for Strain-Driven High-Speed Multi-Axis Optical Scanning,” IEEE Photonics Tech. Lett., vol. 17, pp. 1193-1195, 2005.

Tung, Y.-C., and Kurabayashi, K., “A Single-Layer PDMS-on-Silicon Hybrid Micro Actuator with Multi-Axis Out-of-Plane Motion Capabilities: Part I: Modeling and Design,” J. Microelectromechanical Systems., vol. 14, pp. 548- 557, 2005.

Tung, Y.-C., and Kurabayashi, K. “A Single-Layer Multiple Degree-of-Freedom PDMS-on-Silicon Dynamic Focus Micro-lens,” Proc. the 19h IEEE Micro Electro Mechanical Systems, Istanbul, Turkey, pp. 838-841, Jan. 22 – 26, 2006.

Hsiung, P.-L., Hardy, J., Friedland, S., Soetikno, R., Du, C.B., Wu, A.P., Sahbaie, P., Crawford, J.M, Lowe, A.M., Contag, C.H., and Wang, T.D., “Detection of colonic dysplasia in vivo using a targeted heptapeptide and confocal microendoscopy,” Nature Medicine, vol. 14, pp. 454-458, 2008.

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