Fundamentally new microscopy techniques don’t come out very often, but scientists at the Howard Hughes Medical Institute have just unveiled a new method of “imaging” tissue samples that provides a complex genetic and biomolecular picture of what’s going on inside individual cells.
“It’s an entirely new category of microscopy,” explained Aviv Regev, one of the inventors of the new method. “It’s not just a new technique, it’s a way of doing things that we haven’t ever considered doing before.”
Termed “DNA microscopy,” there are no optical components in the new technique. Instead, it relies on novel chemistry coupled with genome sequencing to identify the precise location of cells and whether they contain certain molecules or genetic sequences.
The team attached samples within a reaction chamber and added a variety of DNA bar codes, which can bind with RNA molecules in a sample, effectively tagging each one. Chemicals are then added to make copies of each tagged molecule, which in turn stick to the sites of DNA bar codes and grow outward in large quantities. The tagged molecules eventually come in contact with each other and link together. Those molecules that are closer together tend to couple more frequently and a DNA sequencer can be used to measure how many of these pairs are in a sample. A computer can then extrapolate the concentrations, and therefore locations, of each of the tagged molecules.
Here’s an animation demonstrating data generated using DNA microscopy, showing the relative location of molecules within a sample:
Study in journal Cell: DNA Microscopy: Optics-free Spatio-genetic Imaging by a Stand-Alone Chemical Reaction