Exploring Spatial Omics Platforms

For decades, technologies like immunohistochemistry (IHC) and in situ hybridization (ISH) have allowed researchers to detect proteins and RNA transcripts in tissues with good spatial resolution. However, traditional methods tend to be time-consuming and single-plex, meaning that they only allow for the analysis of a single biomarker at a time.

More recently, there has been a push toward multiplex approaches to increase the number of biomarkers that can be identified in a single tissue sample. The emerging field of spatial omics combines multiplex approaches, microscopy, and high-throughput technologies to better understand processes taking place in tissues. Although this discipline is in its infancy, it is hoped that spatial omics approaches will one day allow researchers and clinicians to rapidly analyze the entire transcriptome and proteome of a single tissue sample.

As the use of spatial omics has grown, so too has the number of spatial omics platforms. Notable examples include MERSCOPE from Vizgen (for spatial transcriptomics), GeoMx DSP from NanoString Technologies (for spatial profiling), and PhenoCycler from Akoya Biosciences (for multiplexed proteomics). This article will review the top platforms currently available—focusing on the latest advances as of December 2022—and give readers insight into how to select the best technologies for their research needs.

Identifying the obstacles

Although spatial omics is a rapidly evolving discipline, several obstacles currently prevent its widespread use in academic and clinical research. One of the greatest concerns involves cost. Current spatial omics methods require complex instrumentation—including microfluidic devices, custom synthesized bead arrays, and high-resolution fluorescent imaging. Due to the complexity of multi-dimensional analyses, even low-plex spatial assays can reach costs of $1–2K per sample.

Another inherent issue with spatial omics involves clinical scalability. Multiplex analysis is still labor- and time-intensive, and assay throughput is currently limited to 10 to 100 samples per week for many workflows. The underlying bioinformatics processes are also very complicated. Finally, assay standardization is a major concern due to the many steps associated with spatial omics analysis—including sample preparation by pathologists, antibody preparation, staining, scanning, software analysis, and interpretation.

Meet some of the top platforms

Biocompare recently interviewed five companies―Akoya, NanoString Technologies, Resolve Biosciences, Vizgen, and 10x Genomics―to obtain up-to-date information about their latest spatial omics platforms.

As Dr. Ehab El-Gabry, Chief Medical Officer at Akoya, explains, “The PhenoCycler can rapidly image 100 or more biomarkers across whole slides and map every single cell across a tissue section.” And the PhenoCycler continues to deliver impressive results. “At the AGBT [Advances in Genome Biology and Technology] annual conference this year, we also demonstrated the platform’s capability to do multi-omics analysis of both RNA and proteins from the same sample,” El-Gabry points out.

The Akoya PhenoImager HT platform has the same high-speed capabilities as the PhenoCycler for imaging smaller subsets of markers across whole slides. In addition, the PhenoImager can process hundreds of samples per week with high reproducibility and robust data quality. According to El-Gabry, “This is especially crucial for high-throughput translational studies and clinical trials where biomarker signatures need to be analyzed across large cohorts of patient samples.”

NanoString’s GeoMx DSP and CosMx SMI

NanoString’s GeoMx DSP is a high-throughput in situ spatial profiler that allows for the fully automated multi-cellular analysis of whole transcriptomes. As of September 30, 2022, leading researchers from around the world have purchased more than 475 of the company’s spatial biology instruments.

In December of 2022, NanoString announced the first commercial shipments of the CosMx™ Spatial Molecular Imager (SMI) and the AtoMx™ Spatial Informatics Platform (SIP). Vik Devgan, Senior Director of Product Management, Spatial Biology, highlights the advantages of the CosMx SMI. “The CosMx SMI is the first spatial biology platform to provide unprecedented high-plex multi-omics for intact samples at cellular and sub-cellular resolution.” The platform currently enables spatially resolved, digital quantitation of more than 1,000 RNA and over 64 protein targets. Furthermore, the CosMx works with many sample types, including low-quality formalin-fixed paraffin-embedded (FFPE), fresh frozen (FF), and organoid samples.

Resolve Biosciences’ Molecular Cartography

Many customers are choosing the Molecular Cartography workflow because it provides a clear, high-resolution, high-sensitivity, 3D view of subcellular spatial biology. As Paul Steinberg, Chief Commercial Officer at Resolve Biosciences, explains, "Molecular Cartography elucidates the cell’s complex transcriptional landscape without destroying the tissue section or cell culture sample." Over the past year, Resolve Biosciences has run hundreds of projects for customers. In the future, Molecular Cartography is expected to allow for the interrogation of DNA, protein, and metabolic data layers.

Vizgen’s MERSCOPE Platform

MERSCOPE™ (which is powered by MERFISH [multiplexed error-robust fluorescence in situ hybridization] technology) allows users to directly map and quantify the spatial distribution of hundreds of RNA species in situ within individual cells—with no need for downstream sequencing.

George Emanuel, Scientific Co-Founder and Senior Director of Technology and Partnerships at Vizgen, emphasizes that “MERSCOPE is the first high multiplexing, high-resolution, in situ platform to enable true single-cell spatial genomics analysis.” The platform allows users to build custom gene panels through an intuitive web-based portal to specifically address their research questions. Earlier this year, the company also released MERSCOPE Protein Stain Reagent kits, which enable the co-detection of up to 6 proteins and 500 genes from a single sample. MERSCOPE pixel resolution is 100 nm, while the imaging area is relatively large at 1 cm². This high resolution makes it possible to localize specific RNA transcripts within a given cell.

10x Genomics’ Visium and Xenium Platforms

In 2019, 10x Genomics launched Visium, its platform for unbiased spatial discovery. Visium enables researchers to map the whole transcriptome with morphological context in FFPE or fresh frozen tissues. To date, the technology has been cited in more than 365 publications and preprints.

In December of 2022, 10x Genomics announced the commercial launch of its new Xenium platform for in situ analysis, which enables the targeted spatial profiling of genes and proteins at subcellular resolution. The platform includes a versatile and easy-to-use instrument as well as a diverse menu of curated, customizable, and high-quality panels. "We strongly believe Xenium is the best performing system available for in situ analysis. It is yet another example of how we bring together our multidisciplinary expertise, R&D capabilities, and relentless customer focus," said Ben Hindson, Co-Founder and CSO of 10x Genomics.

Conclusions

The field of spatial omics is moving at such an incredible pace that it can be hard to keep track of the latest advances. Fortunately, most of the platforms discussed above are now able to detect both RNA and proteins, while costs are rapidly coming down. Additional factors that may affect your platform choice include plex, resolution, whole-slide capabilities, compatibility with different types of samples, throughput, sensitivity, accuracy, and reproducibility. As these capabilities continue to evolve, spatial omics may one day become a routine part of clinical practice.