Microphotonic Imaging Scanners and Microsystems for Early Cancer Detection

Sponsored by: Wallace H. Coulter Early Career Award in Biomedical Engineering, Tate Foundation, NSF SBIR award (subcontracted from: NanoLite Systems, Inc.), and National Instruments Medical Device Grant Program.

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Handheld Confocal Microscope for Early Cancer Detection

The goal of this research is to develop miniaturized in vivo single fiber optic confocal endoscopes using silicon Micro-Electro-Mechanical systems (MEMS) technologies for the diagnosis of epithelial cancer in the oral cavity. MEMS scanners can be fabricated on a chip-scale and offer an excellent solution for scaling down the system for the endoscope-compatibility.  Two generations of instruments are assembled and tested. The first clinical handheld confocal microscope with 500 micron-diameter micro-mirrors was tested using epithelial tissue cell cultures with embedded gold nanoparticle reflective contrast agents. We further developed larger (1mm diameter) micromirrors, and a new objective system with higher magnification for improved signal-to-noise ratio. We then integrated the new mirrors with the objective system into a 50mm rigid length, 18mm diameter handheld probe with single-cell-layer optical sectioning (5µm axial resolution). We developed a second-generation clinical instrument to be placed for initial clinical testing.

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In Vivo High-Speed 3D Volumetric Optical Coherence Tomography

Optical coherence tomography (OCT) has emerged as a high-resolution diagnostic imaging tool in cases where biopsy is difficult, for image-guided microsurgery, and for three-dimensional pathology reconstruction. Three-dimensional OCT enhances a physician’s visualization of morphology by providing tomographic, microscopic, and en face views simultaneously. Micro-electro-mechanical system (MEMS) technologies offer the unique capability to package micro-optical elements with actuators for imaging in in vivo environments. We have developed a swept source optical coherence tomography (SS-OCT) system incorporating silver-coated two-axis scanning micromirrors for high-speed 3D volumetric imaging of biological specimens. We have acquired real-time in vivo 3D images of human epidermis (Figures C, D) over a 2×1×4 mm3 volume with 12.5µm, 8.6µm lateral resolution at over 9.3 million volume pixels per second. In 2D imaging mode, we can acquired images at faster-than-video (40Hz) frame rates