Tissue clearing

Douglas S. Richardson, Webster Guan, Katsuhiko Matsumoto, Chenchen Pan, Kwanghun Chung, Ali Ertürk, Hiroki R. Ueda, Jeff W. Lichtman

Research output: Contribution to journalReview articlepeer-review

43 Citations (Scopus)


Tissue clearing of gross anatomical samples was first described more than a century ago and has only recently found widespread use in the field of microscopy. This renaissance has been driven by the application of modern knowledge of optical physics and chemical engineering to the development of robust and reproducible clearing techniques, the arrival of new microscopes that can image large samples at cellular resolution and computing infrastructure able to store and analyse large volumes of data. Many biological relationships between structure and function require investigation in three dimensions, and tissue clearing therefore has the potential to enable broad discoveries in the biological sciences. Unfortunately, the current literature is complex and could confuse researchers looking to begin a clearing project. The goal of this Primer is to outline a modular approach to tissue clearing that allows a novice researcher to develop a customized clearing pipeline tailored to their tissue of interest. Furthermore, the Primer outlines the required imaging and computational infrastructure needed to perform tissue clearing at scale, gives an overview of current applications, discusses limitations and provides an outlook on future advances in the field.

Original languageEnglish
Article number84
JournalNature Reviews Methods Primers
Issue number1
Publication statusPublished - 2021 Dec

Bibliographical note

Publisher Copyright:
© 2021, Springer Nature Limited.

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)


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