We have continued to optimize this protocol since doing the experiments in the Macosko et al. Cell paper. What we are sharing here is our current, optimized protocol. As a result, this protocol will not precisely match the methods section of the paper, which is a description of the experiments done in the paper. Please feel free to use these optimizations without author consideration - just acknowledge “helpful advice from Evan Macosko, Melissa Goldman and Steve McCarroll”, and please also include the URL and version number of the protocol in your methods section. This protocol also includes hints, suggestions and images that we could not fit into the the methods section of the paper.