Low Cost, High-Throughput CLARITY Imaging with Single-Cell Resolution and Axon Visualization

Researchers in Prof. Karl Deisseroth's laboratory have developed a low-cost, high-throughput system for high resolution light-sheet imaging to visualize individual cells throughout a volume of intact tissue, including directly visualizing and quantifying the axon tracts of neuronal circuits. This technology enables analysis of large sample cohorts using the CLARITY platform (a process which renders tissue transparent while leaving its cellular structures intact) by accelerating the experimental pipeline and reducing costs by over 90%. In addition, the new process is fully compatible with commercial platforms for imaging and data analysis, further reducing costs and complexity compared to the conventional CLARITY method. When the platform is used for mapping axon projection at micron-level resolution in intact brains, it enables both quantitative analysis of size and intensity/activity as well as direct visualization of region-to-region connectivity. This technology could be used to characterize tissue samples for diagnostics, to perform neuronal circuit analysis for basic neuroscience studies, or to identify cellular targets for therapeutic interventions.
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Stage of Research
The inventors have demonstrated the utility of this technology by combining the high-throughput CLARITY pipeline with the axonal projection mapping to analyze the wiring of the prefrontal cortex in mice. These studies illuminated the logic of information processing in the brain by linking activity during behavior with the molecular properties of neurons.

Intellectual Property
This technology is described in two distinct patent applications, one for the high-throughput imaging system (Stanford Docket S16-092) and one for axonal visualization and quantification (Stanford Docket S16-093).