Single cell genomics has transformed biology by enabling unbiased molecular identification and characterization of the full panoply of cell types that make up a tissue. A 'marriage' between this molecular information, which includes an inventory of all the ligands and receptors expressed by each cell class, and the accompanying 3D spatial information about them will enable the comprehensive reconstruction of the active signaling centers within a given tissue. Here, by continuing a fruitful collaboration between a biologist and molecular biochemist, the Stanford lab works to deliver a transformative new technology for 3D multi-dimensional molecular imaging in intact human tissue. Currently, they are acquiring multiplexed RNA and protein stains of intact lung tissue in 3D, enabled by a ‘one size fits all’ tethering and embedding protocol and using electrophoresis to rapidly transfer staining reagents through large volumes.

They are also developing a new detection strategy to bypass endogenous autofluorescence, low signal to noise, and restriction to five or fewer data channels, by using lanthanide resonant energy transfer. By so doing, they simultaneously overcome challenges in detection of individual signals and massively increase throughput. Furthermore, the technology they deliver will be both biologist 'friendly' and low cost, providing a widely available and practical platform that will be rapidly and broadly adopted by scientists worldwide.