Open AccessMiniature in vivo MEMS-based line-scanned dual-axis confocal microscope for point-of-care pathology
Author(s) -
Chengbo Yin,
Adam K. Glaser,
Steven Y. Leigh,
Y. Chen,
Linpeng Wei,
Prasanth C.S. Pillai,
Mireille Rosenberg,
Sanjeewa Abeytunge,
Gary Peterson,
Christopher Glazowski,
Nader Sanai,
Michael J. Mandella,
Milind Rajadhyaksha,
J. T. C. Liu
Publication year - 2016
Publication title -
biomedical optics express
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.362
H-Index - 86
ISSN - 2156-7085
DOI - 10.1364/boe.7.000251
Subject(s) - microscope , confocal , optics , optical sectioning , materials science , confocal microscopy , lens (geology) , endomicroscopy , microscopy , biomedical engineering , light sheet fluorescence microscopy , depth of field , resolution (logic) , preclinical imaging , optical microscope , frame rate , in vivo , computer science , scanning confocal electron microscopy , artificial intelligence , physics , medicine , scanning electron microscope , microbiology and biotechnology , biology
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.