I will discuss our group’s vision of converting standard off-the-shelf fluorescence microscopy hardware into a tool for spatial omics.
To enable this, I will first introduce technical advancements in DNA-PAINT including approaches that achieve sub-nanometer spatial resolution and spectrally unlimited multiplexing in whole cells. I will then discuss protein labeling probes such as Slow Offrate Modified Aptamers (SOMAmers) that could allow DNA-barcoded labeling of much of the proteome in a cellular environment. Next, I present approaches to increase DNAPAINT’s traditionally slow imaging speeds to achieve throughputs necessary for network-wide molecular interrogation. To this end, we employed rationale DNA sequence design and demonstrate 100-times faster imaging without compromising quality or resolution. Finally, I will present cell surface receptor quantification at thus far elusive resolutions and levels of multiplexing, which could yield insights into the molecular architecture of receptor interactions and enable the future development of “pattern”-based therapeutics.