Bringing Tissue Biology Into 3D: Redefining What’s Possible in Spatial Multiomics
How does seeing tissue in three dimensions change our understanding of cellular organization and interactions?
Spatial biology has rapidly reshaped tissue analysis, but most methods still rely on thin two-dimensional (2D) slices, giving fragmented glimpses of complex tissue structures. As spatial transcriptomics moves toward higher resolution and deeper context, a new question emerges: What becomes possible when scientists can finally see tissues as they exist in three dimensions?
Stellaromics is among the first companies to answer that question. Led by genomics expert Dr. Todd Dickinson—Stellaromics’ CEO and a leader passionate about “building things that matter”—the company has developed Pyxa™.
This 3D spatial multiomics platform was built on the STARmap (spatially-resolved transcript amplicon readout mapping) technology pioneered at Stanford University, MIT, and the Broad Institute. In this article, Dickinson explains how Pyxa enables subcellular‑resolution spatial biology in thick tissue, why 3D matters, and how the technology will shift drug discovery and disease research over the next five years.
Building a 3D spatial platform: The origins of Pyxa
What’s the story behind Stellaromics and the development of Pyxa?
Stellaromics launched in 2022 with the mission to bring powerful new genomics technologies to market. Pyxa, the company’s foundational platform, emerged directly from efforts to translate the academically developed STARmap chemistry into a complete, researcher-ready system.
“The assay produces extremely bright signals that make it possible to image three-dimensional, thick tissue sections at high resolution,” said Dickinson. He noted that this amplified signal was essential in enabling volumetric imaging of intact samples.
He adds that Pyxa was intentionally designed to remove barriers between chemistry, imaging, and informatics: “Pyxa delivers a complete end-to-end solution for 3D spatial transcriptomics,” bringing together sample prep, automated imaging, computational analysis, and visualization in one streamlined workflow.
The platform enables multiplex spatial transcriptomics in tissue sections up to 100 microns, preserving 3D structure and cellular relationships in intact tissue.
What this enables for researchers:
- Pyxa provides an integrated workflow from STARmap sample preparation through 3D visualization.
- Multiplex spatial transcriptomics can now be performed in intact 100 µm tissue sections, preserving cell–cell relationships and tissue architecture
Why 2D isn’t enough: The case for spatial biology in three dimensions
What are the biggest limitations of 2D spatial methods that motivated a 3D approach?
Thin 2D sections can capture broad tissue architecture, but evaluating just 5–10 microns of tissue misses the native spatial relationships between cells and leads to potentially incorrect conclusions.
“Two-dimensional spatial methods rely on thin tissue sections of 5–10 microns, which distort delicate structures and destroy cellular layers,” Dickinson explained.
He noted that this leads to an incomplete picture of many biological systems: “Large cells such as neurons and structures such as vasculature are not fully captured in thin tissue sections… nor is tissue anatomy such as cortical layers in the brain or tumor-stroma interactions.”
By contrast, Pyxa’s ability to image intact thick tissue preserves morphology, cell–cell interactions, and native tissue organization, enabling valuable spatial insights that cannot be achieved using 2D slices.
Key advantages of a 3D approach:
- Preserves cell morphology and long-range interactions lost in 2D sections
- Enables analysis of neurons, vasculature, tumor–stroma interactions, and other complex 3D structures
Inside the Pyxa workflow: From tissue to 3D gene expression map
Can you walk me through a workflow that involves Pyxa?
Pyxa provides an end-to-end workflow encompassing sample prep, chemistry, sequencing, imaging, and analysis. Tissue is sectioned into a 12-well microplate, fixed, and hybridized with SNAIL probes that convert targeted RNA into DNA amplicons carrying gene-specific barcodes.
“STARmap chemistry leverages specific amplification of nucleic acids via intramolecular ligation… to convert target RNA molecules into DNA amplicons with gene-specific codes,” said Dickinson.
Multiple rounds of sequencing by ligation occur directly on‑instrument. Dickinson highlights the precision of the readout: “Decoding probes transiently bind to the target DNA and ligate to form a stable product for imaging only when a perfect match occurs, which eliminates error accumulation.”
Credit: Stellaromics.
Primary data is automatically processed, so researchers can explore gene expression in 3D using PyxaStudio™ or export it for analysis with open-source tools.
What researchers gain from the workflow:
- Fully automated fluidics, sequencing, and volumetric imaging
- A streamlined workflow from raw data to 3D visualization and quantification
Imaging thick tissue: Performance, resolution, and practical limits
How does performance scale with sample thickness?
Pyxa’s imaging system was purpose-built to analyze thick tissue. Its confocal volumetric optics and reagent penetration ensure that signal quality can be achieved uniformly throughout the tissue. According to Dickinson: “Pyxa is capable of imaging tissue sections up to 100 µm and detecting subcellular transcript localization with sub-micron resolution.”
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Dickinson explains that housing the entire workflow—sample prep, sequencing, and imaging—in the same 12-well plate “allows for penetration of the reagents through the entire tissue volume and ensures a consistent gradient of amplicon generation.”
Practical capabilities at a glance:
- Designed specifically for thick tissue while maintaining signal quality
- Achieves sub-micron resolution for transcript-level spatial localization
Biological questions unlocked by 3D spatial multiomics
What biological questions do you feel Pyxa is uniquely suited to address?
The ability to visualize entire tissue volumes allows researchers to interrogate rare cell populations, structural niches, and signaling interactions more accurately.
“Using Pyxa, researchers can now detect rare cell types, map long-range cell interactions, and measure cell‒cell signaling in situ in ways that were previously impossible using 2D spatial transcriptomics techniques.”
Early adopters are already applying Pyxa in oncology to assess spatial biomarkers, in Alzheimer’s research to explore cellular niches around amyloid beta plaques, and in drug development to evaluate effects in situ.
Stellaromics recently announced the installation of the first Pyxa instrument at the University of Glasgow in the laboratory of Dr. Nigel Jamieson, whose team uses spatial transcriptomics approaches to investigate cancer and inflammatory disease. Using the system, Jamieson’s team plan to examine the spatial dynamics of cancer cells and their interactions with the tumor microenvironment.
“Pyxa opens a new window into how tumors interact, co-opt and invade their surrounding tissues, blood vessels and nerves… We believe this approach will overcome longstanding challenges in capturing tissue morphology and avoiding cellular misassignment, particularly within the intense environment of tumors, including glioblastoma, pancreatic cancer, and colorectal cancer as they invade healthy tissue," said Jamieson in a press release announcing the installation.
In the United States, Stellaromics installed its first Pyxa system at the University of California, Irvine, in Dr. Rui Chen's laboratory. Chen is a globally recognized vision researcher and plays a key role in the global, collaborative Human Cell Atlas initiative. His team is constructing detailed 3D spatial atlases of the human eye and trigeminal ganglion (a cluster of neurons that acts as a relay station for sensory information from the face) to advance understanding of sensory systems at single-cell resolution, while also developing new drugs for retinal degenerative diseases.
A second Pyxa has been installed at Emory University in Dr. Hailing Shi’s laboratory. Dr. Shi has deep expertise in spatial technology development and contributed to the early development of STARmap methods. Her team is dedicated to uncovering the principles of context-dependent RNA regulation that underlie brain physiology and function, integrating nucleic acid chemistry, spatial genomics, and computation.
“Pyxa moves beyond simple cell atlasing to answer functional questions about how spatial architecture drives disease onset, progression, and therapeutic response,” said Dickinson.
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Scientific opportunities enabled by 3D:
- Supports functional analysis of how spatial architecture shapes disease
- Facilitates target validation and in situ drug evaluation
The future of 3D spatial transcriptomics
In five years, how do you hope Pyxa or 3D spatial multiomics will have transformed biology or medicine?
Dickinson anticipates that 3D spatial multiomics will evolve from an exploratory research tool into a core component of translational science and clinical development.
He believes volumetric spatial data will be essential for validating therapeutic mechanisms and informing precision medicine strategies: “Its ability to map drug efficacy and local gene expression at subcellular resolution will be critical for validating therapeutic mechanisms of action.”
He’s particularly excited for its potential in the cell and gene therapy space: “By evolving from 2D snapshots to comprehensive 3D disease atlases, researchers will gain the contextual data necessary to identify novel biomarkers and stratify patient populations.
“This transformation will embed spatial multiomics into the standard of care, bridging the gap between biological insights and the delivery of next-generation precision medicines.”
Predicted impact on biomedicine:
- 3D spatial insights will support clinical trial design and therapeutic validation
- Spatial multiomics will become integrated into standard precision‑medicine workflows
In summary, the ability to perform 3D spatial multiomics in intact tissue sections is redefining how researchers understand tissues by preserving native tissue architecture and spatial context. “Pyxa will transform biology by turning 3D spatial multiomics from an exploratory tool into a driver of clinical development,” said Dickinson.
Key takeaways:
- Thick‑tissue, subcellular‑resolution imaging enables questions impossible in 2D
- Integrated chemistry, imaging, and analysis streamline the path to 3D insights
- Volumetric spatial data informs drug discovery and translational research
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