Combined measurement of diverse molecular and anatomical traits that span multiple levels, from molecules to cells to an entire system, remains a major challenge in biology. In this talk, I will introduce a series of technologies including CLARITY, SWITCH, and stochastic electrotransport that enable proteomic imaging for scalable, integrated, high-dimensional phenotyping of both animal tissues and human clinical samples. The method, termed SWITCH, uniformly secures tissue architecture, native biomolecules, and antigenicity across an entire system by synchronizing the tissue preservation reaction. The heat- and chemical-resistant nature of the resulting framework permits virtually unlimited rounds of relabeling of a single tissue with precise co-registration of multiple datasets. Furthermore, SWITCH synchronizes labeling reactions to improve probe penetration depth and uniformity of staining. With SWITCH, we demonstrated combinatorial protein expression profiling and high-dimensional quantitative analysis of the human cortex. Such integrated high-dimensional information may accelerate our understanding of biological systems at multiple levels.
