Striving for higher res imaging of cells, Harvard team debuts startup with backing from ARCH, Northpond
As scientists race to find new ways to look into what’s going on inside cells, ARCH Venture Partners and Northpond Ventures are injecting $14 million into a Harvard team promising to visualize activity on a “subcellular level” — down to every RNA.

Xiaowei Zhuang and David Walt are two of the prominent scientists behind Vizgen. Zhuang, a Howard Hughes Medical Institute Investigator and Harvard professor, was the inventor of another popular super-resolution microscopy method while David Walt was a scientific founder of the sequencing giant Illumina.
Vizgen was founded on MERFISH, or multiplexed error-robust fluorescence in situ hybridization, which was invented by Jeffrey Moffitt while he was a postdoc at Zhuang’s lab. MERFISH is, in turn, built on FISH — a technology that’s been used for decades to detect DNA or RNA targets by sending fluorescent probes to bind to them.

The new imaging technology leverages new error detection and correction techniques, including barcoding schemes and combinatorial labeling and imaging, to achieve higher accuracy and save time.
As a result, it allows scientists to investigate many more RNA species, according to the company.
“Given its ability to quantify RNAs across a wide range of abundances without amplification bias while preserving native context, we envision that MERFISH will enable many applications of in situ transcriptomic analyses of individual cells in culture or complex tissues,” Zhuang and Moffitt wrote with collaborators in a paper introducing the tech in 2015.
Walt further explained why that’s useful in an interview with Xconomy:
Every image that’s taken as a consequence of the way that this process is done is done with approximately 100 nanometers of resolution, so you can zoom out all the way to the whole tissue and see where the gene expression is occurring, then you can zoom in to a single cell and look at the subcellular expression of every one of those RNAs that are present in the sample.

That can tell researchers a lot about cell type, state, organization, interactions as well as function within the tissue.
“The deep information unlocked by MERFISH exposes biology at the network level, driving insights that will help us build the future of human health,” Keith Crandell, managing director at ARCH, said in a statement.