Hoping to overcome the light scattering effects that have limited imaging into 3D tissue volumes, researchers have worked for more than a century to develop clearing techniques.1 But as Richardson and Lichtman detailed, "a large number of recent innovations" have advanced the work.
Even more recently, commercial developers have begun to invest in cleared tissue imaging, as two recent announcements demonstrate.
At the 2016 Society for Neuroscience annual meeting, Applied Scientific Instrumentation (ASI) announced the Immersion Objective for Cleared Tissue, a new microscope objective optimized for light-sheet imaging of tissue processed with an agent such as CLARITY (developed by Stanford University's Karl Deisseroth, MD, Ph.D., and colleagues) or Scale (developed by the RIKEN Brain Science Institute in Japan). The objective was designed to work with both commercial and home-built systems.
Also, an exclusive, worldwide license agreement with Stanford University—providing exclusive intellectual property rights for inventions related to both SPED (SPherical-aberration-assisted Extended Depth-of-field) microscopy and new technology that enables multiplexed, volumetric visualization of long and short RNAs in intact tissue—will bring these technologies to market. The company developing this product platform, ClearLight Diagnostics, LLC (Sunnyvale, CA), was founded by Deisseroth. Through commercialization, the company aims to improve diagnosis and treatment of a wide range of diseases—beginning with cancer.
Detailed in an article by researchers in the Columbia University lab of Raju Tomer, who previously worked with Deisseroth, SPED combines the large volumetric field of view of an extended depth of field with the optical sectioning of light sheet microscopy, and thereby eliminates the need to physically scan the detection objective while maintaining spatial resolution. At its core is a scalable method for extending depth of field by building upon the optical mechanisms that induce spherical aberrations.
The RNA interrogation technology promises versatile, high-content, and scalable molecular phenotyping of intact tissues that retains RNAs in clarified tissue—plus amplification tools for multiplexed detection. According to ClearLight, nucleic acid labeling in cleared tissue has important potential for research and clinical work, because it allows detection of both diverse coding and non-coding RNA variants.
The commercialization of enabling products will push tissue clearing into the mainstream, and help to realize Richardson and Lichtman's portension of "many new discoveries and a more spatially integrated view of the inner workings of organisms."
REFERENCE
1. D. S. Richardson and J. W. Lichtman, Cell, 162, 2, 246–257 (Jul. 16, 2015); doi:10.1016/j.cell.2015.06.067.
