A Deep Dive into Spatial platforms MERFISH, CosMx SMI, STOmics, Xenium, and Visium HD

helixhorizonsoluti
Mar 29
3 min read

Spatial organization of cells in a tissue slide

Spatial biology has transformed our comprehension of cellular interactions and tissue structure. Cutting-edge developments in spatial platforms now allow scientists to view and examine biological samples with exceptional clarity. This article delves into the functionalities of MERFISH, CosMx, STOmics, Xenium, and Visium HD, emphasizing their contributions to tissue imaging and the understanding they offer into intricate biological systems.

Introduction to Spatial Biology

Spatial biology aims to comprehend the spatial arrangement of cells within tissues, which is essential for unraveling cellular interactions, signaling pathways, and disease mechanisms. Conventional methods frequently do not provide the spatial resolution required to accurately capture these interactions. Nonetheless, with the development of advanced spatial platforms, researchers are now able to map cellular heterogeneity and tissue architecture at the single-cell level.

MERFISH: Multiplexed Error-Robust Fluorescence In Situ Hybridization

Technology:

MERFISH (Vizgen) uses combinatorial barcoding and sequential hybridization to image thousands of RNA species in situ.
Achieves ~0.5 µm resolution with >99% detection accuracy via error-robust encoding schemes.

Applications:

Cell typing in dense tissues (e.g., brain, liver).
Spatial cell-cell communication networks.

CosMx Spatial Molecular Imager (SMI): Ultra-High-Plex RNA and Protein Imaging

Technology:

CosMx SMI by NanoString combines RNA and protein detection in the same tissue section using cyclic fluorescence in situ hybridization (FISH).
RNA detection: Targets up to 1,000 RNA transcripts per cycle with subcellular resolution (0.1–0.5 µm/pixel).
Protein detection: Uses oligonucleotide-conjugated antibodies to detect up to 100 proteins simultaneously.
Workflow: Sequential hybridization and imaging cycles enable ultra-high plex analysis.

Applications:

Ideal for tumor microenvironment studies, immune cell interactions, and cell-state heterogeneity in FFPE or fresh-frozen tissues.
Example: Mapping immune checkpoint proteins (e.g., PD-L1) alongside RNA signatures in cancer.

STOmics (Stereo-seq): Ultra-Large Field-of-View Spatial Transcriptomics

Technology:

STOmics Stereo-seq (BGI) uses DNA nanoball-patterned chips for cm²-scale spatial transcriptomics with 0.5–1 µm resolution.
Captures whole-transcriptome data (~20,000 genes) across large tissue sections (up to 13 x 13 cm).
Combines in situ sequencing with spatial barcoding for high-density molecular cartography.

Applications:

Developmental biology (e.g., embryonic organogenesis).
Disease mapping in complex tissues like brain or heart.

Xenium (10x Genomics): In Situ Transcriptomics with High-Plex RNA Detection

Technology:

Xenium is a multiplexed FISH-based platform for in situ RNA detection with subcellular resolution (0.5 µm/pixel).
Detects hundreds to thousands of RNA targets in a single tissue section.
Integrates with Visium HD for multi-omic workflows (e.g., combining whole-transcriptome data with targeted gene panels).

Applications:

Neuroscience: Mapping neuronal subtypes and synaptic RNA localization.
Oncology: Profiling tumor-immune interactions at single-cell resolution.

Visium HD (10x Genomics): High-Definition Spatial Transcriptomics

Technology:

Visium HD builds on the original Visium platform, offering 2 µm resolution (vs. 55 µm in standard Visium) via microarray-based spatial barcoding.
Captures whole-transcriptome data (18,000+ genes) with near-single-cell resolution.
Compatible with FFPE and fresh-frozen tissues, with optimized protocols for challenging samples.

Applications:

Precision oncology: Identifying rare tumor subclones and metastatic niches.
Cell atlas construction: Resolving fine-grained cell states in complex tissues.

Comparison of Key Features

Platform	Plex (RNA/Protein)	Resolution	Tissue Compatibility	Key Strength
MERFISH	1,000+ RNAs	0.5 µm	Fresh-frozen	Ultra-high RNA plex
CosMx SMI	1,000 RNAs + 100 proteins	0.1–0.5 µm	FFPE/fresh-frozen	Multi-omics (RNA + protein)
STOmics Stereo-seq	20,000 RNAs	0.5–1 µm	Fresh-frozen	cm²-scale imaging
Xenium	1,000+ RNAs	0.5 µm	FFPE/fresh-frozen	Targeted panels + scalability
Visium HD	18,000 RNAs	2 µm	FFPE/fresh-frozen	Whole-transcriptome HD mapping

Conclusion

These platforms are redefining spatial biology by addressing distinct challenges:

CosMx SMI and Xenium excel in targeted, high-plex RNA/protein detection for hypothesis-driven studies.
STOmics Stereo-seq and Visium HD enable unbiased whole-transcriptome mapping at unprecedented scales.
MERFISH remains a gold standard for ultra-high-plex RNA imaging in research settings.

By integrating these tools, researchers can dissect spatial heterogeneity, decode cellular ecosystems, and accelerate discoveries in precision medicine.

This version corrects inaccuracies and adds technical depth while maintaining readability. Let me know if you’d like further refinements!