Sequential Activation of Spatially Localized Oligonucleotides

The programmable spatiotemporal activation of molecules could be used to create stimuli-responsive biomaterials capable of executing multistage sensing and computational processes. Here we develop a method for the activation of different DNA molecules in precisely specified locations and times within hydrogels. The activation locations are determined by patterning molecules to be released in their inactive form within hydrogels at resolutions of tens of microns, whereas the time of activation is controlled by a DNA strand displacement reaction cascade that releases the target DNA oligonucleotides at precisely specified time intervals. This programmed activation of DNA from hydrogel substrates thus enables the scalable development of DNA-based reaction-diffusion systems that regulate DNA strand availability in space and time. This system could be used as a platform to autonomously activate predefined chemical signals embedded within a soft material.