MERSCOPE is a large benchtop instrument composed of two pieces. The imaging cycles run over 24 hours are fully automated, but sample prep stretches over two days and involves some manual steps. However, multiple samples can be processed in parallel. Samples can be fresh/frozen or FFPE, though FFPE data quality can be somewhat degraded depending on the quality of the RNA present in the sample-- an area of continuing development by the company. More than 25 human and mouse tissue types have been put through the paces, and the system has also been used with Drosophila and zebrafish tissues as well.
MERFISH, invented in Xiaowei Zhuang's lab, is a repetitive probing scheme detecting individual RNA molecules. Probes bound to the targets have overhangs which can bind to labeled probes. In each round of probing, a given original probe will either bind or not bind labeled probes, providing one binary bit of information. The barcode probing scheme includes error correction to ensure high fidelity, robust detection of targeted transcripts. Each targeted transcript has multiple probes, enhancing sensitivity.
Resolution of the system is 100 nanometers -- true subcellular resolution. Sensitivity to detect a molecule can be close to 100% in dissociated cells or cell line material; intact tissues have about 70%, higher than other spatial analysis platforms. At this time the company is only offering RNA detection, but in the future this will be joined by proteins via DNA-linked antibodies. Data is output in standard CSV and TIFF formats which can be used with the company's own tools or a wide array of open source packages.
In his AGBT presentation Lo showed using MERSCOPE data to fluidly move between single cell information to cluster and identify cell types and the MERSCOPE images showing those single cell identities in a spatial context. Lo also showed the effect of sensitivity on analysis, showing a low copy number gene which at low sensitivity appears to have no spatial clustering but has a very strong spatial gradient in a mouse brain section when measured on MERSCOPE. In another example he showed that MERSCOPE can image over 20,000 cells in sample, enabling very rare cell types to be detected and profiled for hundreds of genes.
Lo closed his talk by giving the detailed launch plans, with beta instruments already in the field and a limited U.S. launch this summer, with full production expected before end-of-year.