Handheld histology-equivalent sectioning laser-scanning confocal optical microscope for interventional imaging
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A handheld, forward-imaging, laser-scanning confocal microscope (LSCM) demonstrating optical sectioning comparable with microtome slice thicknesses in conventional histology, targeted towards interventional imaging, is reported. Fast raster scanning (~2.5 kHz line scan rate, 3.0–5.0 frames per second) was provided by a 2-axis microelectromechanical system (MEMS) scanning mirror fabricated by a method compatible with complementary metal-oxide-semiconductor (CMOS) processing. Cost-effective rapid-prototyped packaging combined the MEMS mirror with micro-optical components into a probe with 18 mm outer diameter and 54 mm rigid length. ZEMAX optical design simulations indicate the ability of the handheld optical system to obtain lateral resolution of 0.31 and axial resolution of 2.85 µm. Lateral and axial resolutions are experimentally measured at 0.5 µm and 4.2 µm respectively, with field of view of 200 × 125 µm. Results of reflectance imaging of ex vivo swine liver, and fluorescence imaging of the expression of cytokeratin and mammaglobin tumor biomarkers in epithelial human breast tissue from metastatic breast cancer patients are presented. The results indicate that inexpensive, portable handheld optical microscopy tools based on silicon micromirror technologies could be important in interventional imaging, complementing existing coarse-resolution techniques to improve the efficacy of disease diagnosis, image-guided excisional microsurgery, and monitored photodynamic therapy.
KeywordsHandheld instrumentation Laser scanning confocal microscope (LSCM) CMOS-compatible scanning micromirror Microelectromechanical systems (MEMS) Interventional imaging
Financial support of this research by Wallace H Coulter Foundation Early Career Award is gratefully acknowledged. The scanning micromirrors were fabricated at Stanford Nanofabrication Facility and the Microelectronics Research Center at the University of Texas at Austin, both supported by the National Science Foundation National Nanofabrication Infrastructure Network under grants 9731293 and 0335765, respectively. The University of Texas M. D. Anderson Cancer Center and University of Texas Southwestern Tissue Repository at UTSW provided the swine liver and human specimens used for this research respectively. Control images for the fluorescence microscopy experiments were obtained using equipment at the Core facilities within the Institute for Cellular and Molecular Biology at the University of Texas at Austin.
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