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Proceedings Paper

3D on-chip microscopy of optically cleared tissue
Author(s): Yibo Zhang; Yoonjung Shin; Kevin Sung; Sam Yang; Harrison Chen; Hongda Wang; Da Teng; Yair Rivenson; Rajan P. Kulkarni; Aydogan Ozcan
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Paper Abstract

Traditional pathology relies on tissue biopsy, micro-sectioning, immunohistochemistry and microscopic imaging, which are relatively expensive and labor-intensive, and therefore are less accessible in resource-limited areas. Low-cost tissue clearing techniques, such as the simplified CLARITY method (SCM), are promising to potentially reduce the cost of disease diagnosis by providing 3D imaging and phenotyping of thicker tissue samples with simpler preparation steps. However, the mainstream imaging approach for cleared tissue, fluorescence microscopy, suffers from high-cost, photobleaching and signal fading. As an alternative approach to fluorescence, here we demonstrate 3D imaging of SCMcleared tissue using on-chip holography, which is based on pixel-super-resolution and multi-height phase recovery algorithms to digitally compute the sample’s amplitude and phase images at various z-slices/depths through the sample. The tissue clearing procedures and the lens-free imaging system were jointly optimized to find the best illumination wavelength, tissue thickness, staining solution pH, and the number of hologram heights to maximize the imaged tissue volume, minimize the amount of acquired data, while maintaining a high contrast-to-noise ratio for the imaged cells. After this optimization, we achieved 3D imaging of a 200-μm thick cleared mouse brain tissue over a field-of-view of <20mm2 , and the resulting 3D z-stack agrees well with the images acquired with a scanning lens-based microscope (20× 0.75NA). Moreover, the lens-free microscope achieves an order-of-magnitude better data efficiency compared to its lens-based counterparts for volumetric imaging of samples. The presented low-cost and high-throughput lens-free tissue imaging technique enabled by CLARITY can be used in various biomedical applications in low-resource-settings.

Paper Details

Date Published: 13 February 2018
PDF: 10 pages
Proc. SPIE 10485, Optics and Biophotonics in Low-Resource Settings IV, 104850Z (13 February 2018); doi: 10.1117/12.2290558
Show Author Affiliations
Yibo Zhang, Univ. of California, Los Angeles (United States)
Yoonjung Shin, David Gellen School of Medicine, Univ. of California, Los Angeles (United States)
Kevin Sung, Univ. of California, Los Angeles (United States)
Sam Yang, Univ. of California, Los Angeles (United States)
Harrison Chen, Univ. of California, Los Angeles (United States)
Hongda Wang, Univ. of California, Los Angeles (United States)
Da Teng, Univ. of California, Los Angeles (United States)
Yair Rivenson, Univ. of California, Los Angeles (United States)
Rajan P. Kulkarni, David Gellen School of Medicine, Univ. of California, Los Angeles (United States)
Jonsson Comprehensive Cancer Ctr., Univ. of California, Los Angeles (United States)
Aydogan Ozcan, David Gellen School of Medicine, Univ. of California, Los Angeles (United States)


Published in SPIE Proceedings Vol. 10485:
Optics and Biophotonics in Low-Resource Settings IV
David Levitz; Aydogan Ozcan; David Erickson, Editor(s)

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