Tissue labeling and clearing technologies allow unrivaled imaging of intact biological specimens at sub-cellular resolutions. However, so far, they could only be applied on the tissues of organisms with no more than several months of age such as mouse or human embryos but not decades-aged intact human organs. A major problem has been the sturdy nature of decades-aged human tissue. The accumulation of opaque and dense molecules such as lipofuscin and non-soluble collagen impede penetration of chemicals deep into human organs and, thereby block both clearing and labeling of human specimens larger than a few millimeters.

We introduce SHANEL for molecular and cellular profiling of intact human organs. SHANEL relies on a new tissue permeabilization chemistry that enables labeling and clearing of centimeters size human organs. We used SHANEL to generate the first intact transparent adult human brain and kidney, and perform 3D histology using antibodies and dyes in centimeters depth, a ~2-3 orders of magnitude scaling up. We revealed structural details of the sclera, iris and suspensory ligament in the human eye, and the vessels and glomeruli in the human kidney. We also applied SHANEL on transgenic pig organs to map complex structures of EGFP expressing beta cells in >10 cm size pancreas. Thus, SHANEL could accelerate large scale mapping/phenotyping projects such as the Human Protein Atlas, Human Brain Mapping and Brain Initiative. In addition, as the first technology to generate cellular details of intact human organs, it could facilitate tissue engineering studies, especially by 3D-bioprinting, which requires detailed blueprints (3D maps) of organs to be replicated.