All biological systems are intrinsically and intricately spatially organised. Over the last two decades, spatial biologics has shifted from bulk sequencing to single-cell sequencing. There has been a huge level of excitement surrounding spatial methods recently, with spatial proteomics being hailed as the ‘Method of the Year’ by Nature in 2024.
Alex Genshaft, Product Manager at Vizgen explained that Vizgen has recently partnered with Ultivue to explore the clinical market in more detail and deliver on their promises to the wider patient community. Genshaft stated that he uses three main platform technologies: the InSituPlex at STARVUE, MERFISH 2.0, and MERSCOPE Ultra. His talk mainly focused on the MERFISH 2.0 and MERSCOPE Ultra.
MERSCOPE Ultra provides high-resolution imaging with subcellular resolution, enabling detailed intracellular analysis and accelerated data processing. Genshaft mentioned that MERSCOPE works with 60X or 40X objectives and achieves subcellular resolution. Furthermore, this PROFILING can be scaled up to 1000 genes with fully custom panels. Genshaft also emphasised the speed of the technology and the fact that it processes data quickly and generates the files immediately which saves scientists from transporting them to the cloud and dealing with extra regulations and so forth.
MERFISH 2.0 reveals cellular heterogeneity in impressive detail and enables scientists to map the spatial organisation of cell types. With lower-quality RNA, there are fragmentations and breaks meaning it becomes more difficult to reacquire those samples or reacquire those transcripts. MERFISH 2.0 and the company’s FFPE protocol have two main benefits that help tackle this. Firstly, the MERFISH optimises the encoding probe design which enables more efficient occupancy at every probe site. Secondly, they have augmented the readout probe structure which drives higher intensity and translates to more transcripts.
Vizgen’s platforms outperform competitors in sensitivity and specificity, as shown in normalized benchmarking studies. The MERFISH 2 showed a 2 – 8-fold increase in transcript detection depending on tissue detection and fewer cells dropped out of MERFISH 2 upon filtering. Also, there is high reproducibility and correlation across replicates and between MERFISH 1 and 2 confirming data reliability. Overall, the introduction of MERFISH 2.0 has brought substantial improvements in sensitivity and specificity. This enables higher transcript detection and better cell type discovery, particularly in degraded samples.
These platforms displayed improvements across a range of tissues including ovarian, breast, and brain cancers. Genshaft commented that the detection of immune cells and rare cell types facilitates deeper insights into cell-cell interactions and spatial enrichment. In conclusion, these advancements in spatial transcriptomics and proteomics seek to enhance patient care and drive efficiency in clinical research, with promising results in cancer studies.
