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Published May 2018 | Accepted Version + Supplemental Material
Journal Article Open

Hydrogel-Tissue Chemistry: Principles and Applications


Over the past five years, a rapidly developing experimental approach has enabled high-resolution and high-content information retrieval from intact multicellular animal (metazoan) systems. New chemical and physical forms are created in the hydrogel-tissue chemistry process, and the retention and retrieval of crucial phenotypic information regarding constituent cells and molecules (and their joint interrelationships) are thereby enabled. For example, rich data sets defining both single-cell-resolution gene expression and single-cell-resolution activity during behavior can now be collected while still preserving information on three-dimensional positioning and/or brain-wide wiring of those very same neurons—even within vertebrate brains. This new approach and its variants, as applied to neuroscience, are beginning to illuminate the fundamental cellular and chemical representations of sensation, cognition, and action. More generally, reimagining metazoans as metareactants—or positionally defined three-dimensional graphs of constituent chemicals made available for ongoing functionalization, transformation, and readout—is stimulating innovation across biology and medicine.

Additional Information

© 2018 Annual Reviews. We thank Prof. Kwanghun Chung, Prof. Zhenan Bao, Dr. Ritchie Chen, Dr. Xiao Wang, Dr. Emily Sylwestrak, and members of our laboratories for helpful comments on the manuscript. K.D. is supported by the National Institutes of Health (NIH) R01DA03537701, R01MH075957, and R01MH086373, as well as by the Defense Advanced Research Projects Agency and Army Research Laboratory NeuroFAST program (Cooperative Agreement W911NF-1420013). V.G. is supported by the NIH via the New Innovator Award DP2NS087949 and the Presidential Early Career Award for Science and Engineers, OT2OD023848–01, and R01AG047664; V.G. is also a Heritage Medical Research Institute Investigator and director of the Center for Molecular and Cellular Neuroscience in the Chen Institute at Caltech. Disclosure Statement: All protocols, software, and other information regarding these methods is freely available from the authors and online, and disseminated via free hands-on training courses (clarityresourcecenter.org and clover.caltech.edu). V.G. and K.D. have disclosed intellectual property regarding HTC methods to Caltech and Stanford, some of which has been licensed to ClearLight Diagnostics, which is exploring applications for cancer diagnostics, and with which there are consulting arrangements and equity; V.G. and K.D. each also have grant support from the US federal government (National Institutes of Health and National Science Foundation) to further develop, apply, and disseminate these methods.

Attached Files

Accepted Version - nihms-1001920.pdf

Supplemental Material - bb47_deisseroth_supfig1.pdf


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August 19, 2023
October 18, 2023