title: Miniature in vivo MEMS-based line-scanned dual-axis confocal microscope for point-of-care pathology.
abstract: There is a need for miniature optical-sectioning microscopes to enable in vivo interrogation of tissues as a real-time and noninvasive alternative to gold-standard histopathology. Such devices could have a transformative impact for the early detection of cancer as well as for guiding tumor-resection procedures. Miniature confocal microscopes have been developed by various researchers and corporations to enable optical sectioning of highly scattering tissues, all of which have necessitated various trade-offs in size, speed, depth selectivity, field of view, resolution, image contrast, and sensitivity. In this study, a miniature line-scanned (LS) dual-axis confocal (DAC) microscope, with a 12-mm diameter distal tip, has been developed for clinical point-of-care pathology. The dual-axis architecture has demonstrated an advantage over the conventional single-axis confocal configuration for reducing background noise from out-of-focus and multiply scattered light. The use of line scanning enables fast frame rates (16 frames/sec is demonstrated here, but faster rates are possible), which mitigates motion artifacts of a hand-held device during clinical use. We have developed a method to actively align the illumination and collection beams in a DAC microscope through the use of a pair of rotatable alignment mirrors. Incorporation of a custom objective lens, with a small form factor for in vivo clinical use, enables our device to achieve an optical-sectioning thickness and lateral resolution of 2.0 and 1.1 microns respectively. Validation measurements with reflective targets, as well as in vivo and ex vivo images of tissues, demonstrate the clinical potential of this high-speed optical-sectioning microscopy device.
authors.affiliation: University of Washington, Department of Mechanical Engineering, Seattle, WA 98195, USA.
authors.forename: C
authors.initials: C
authors.lastname: Yin
authors.affiliation: University of Washington, Department of Mechanical Engineering, Seattle, WA 98195, USA.
authors.forename: A K
authors.initials: AK
authors.lastname: Glaser
authors.affiliation: University of Washington, Department of Mechanical Engineering, Seattle, WA 98195, USA.
authors.forename: S Y
authors.initials: SY
authors.lastname: Leigh
authors.affiliation: University of Washington, Department of Mechanical Engineering, Seattle, WA 98195, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.affiliation: University of Washington, Department of Mechanical Engineering, Seattle, WA 98195, USA.
authors.forename: L
authors.initials: L
authors.lastname: Wei
authors.affiliation: University of Washington, Department of Mechanical Engineering, Seattle, WA 98195, USA.
authors.forename: P C S
authors.initials: PC
authors.lastname: Pillai
authors.affiliation: University of Washington, Department of Mechanical Engineering, Seattle, WA 98195, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Rosenberg
authors.affiliation: Memorial Sloan-Kettering Cancer Center, Dermatology Services, Department of Medicine, New York, NY 10010, USA.
authors.forename: S
authors.initials: S
authors.lastname: Abeytunge
authors.affiliation: Memorial Sloan-Kettering Cancer Center, Dermatology Services, Department of Medicine, New York, NY 10010, USA.
authors.forename: G
authors.initials: G
authors.lastname: Peterson
authors.affiliation: Memorial Sloan-Kettering Cancer Center, Dermatology Services, Department of Medicine, New York, NY 10010, USA.
authors.forename: C
authors.initials: C
authors.lastname: Glazowski
authors.affiliation: Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013 USA.
authors.forename: N
authors.initials: N
authors.lastname: Sanai
authors.affiliation: Stanford University School of Medicine, Department of Pediatrics, Stanford, CA 94305, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Mandella
authors.affiliation: Memorial Sloan-Kettering Cancer Center, Dermatology Services, Department of Medicine, New York, NY 10010, USA.
authors.forename: M
authors.initials: M
authors.lastname: Rajadhyaksha
authors.affiliation: University of Washington, Department of Mechanical Engineering, Seattle, WA 98195, USA.
authors.forename: J T C
authors.initials: JT
authors.lastname: Liu
keywords: (170.1790) Confocal microscopy; (170.2520) Fluorescence microscopy; (170.3880) Medical and biological imaging; (170.5810) Scanning microscopy; (230.4685) Optical microelectromechanical devices