TMA Construction for Xenium Success in 5 Easy Steps

The Spatial Bottleneck No One Talks About

Mundane as it sounds, cutting-edge platforms like the 10x Genomics Xenium® Spatial Analyzer rely on effective, meticulous, and high quality sample preparation to be successful. 

As biologists, many of us are familiar with the attention to detail and tedious specifics required to achieve the big-picture, sexy discoveries. Spatial technologies like Xenium Prime 5k are revolutionizing our understanding of how gene expression varies within the complex architecture of tissues. Unfortunately, incomplete fixation, hidden necrosis, or mis-picked tissue regions quietly sabotage expensive runs, leaving you with patchy transcripts and false negatives. Without upstream tissue-quality assessment and array architecture, even the fanciest technology may suffer from a lack of data fidelity.

BioChain closes that gap. Our integrated tissue quality assessment to custom tissue-microarray (TMA) construction pipeline ensures every core you profile actually represents the biology you care about. Let’s talk about it.

Why Tissue Quality Is the First Variable in Every Xenium Equation

Look. It’s just a matter of statistics: the more diverse your array, the trickier it becomes to accurately represent all of it.

Tissue heterogeneity remains a challenge in histopathology and spatial research. Variations in cellular composition, disease progression, and spatial distribution of biomarkers make it difficult to capture the full picture with a single sample. Deviations in tissue sampling can skew results, leading to misinterpretation or even erroneous conclusions. Sub-optimal fixation, necrosis, or off-target punching all translate into patchy transcripts, noisy segmentation, and expensive re-runs. Xenium’s own sample-prep group warns that tissue QC (with H&E) is critical for sample selection, and that poorly processed blocks or mismatched float-times will derail an otherwise perfect run.

For any FFPE section you intend to profile, there are some key things to look out for:

  • Histology first. Verify morphology and RNA integrity before you touch a microtome.

  • Match the capture window. Xenium scan region spans 10.5mm x 22.5mm window; anything larger leads to tissue loss or unusable empty space.

Minimise heat and re-embedding stress. Even short temperature spikes raise gDNA and erode assay sensitivity.

BioChain’s Five-Step Workflow for Xenium-Ready TMAs

At BioChain, we understand that the accuracy of TMAs is the cornerstone of downstream spatial analysis. That’s why we’ve made it our mission to integrate expert TMA construction services into our in-house Xenium workflow in a way that will ensure your every sample is as representative as possible. Our expertise means we know some of the common pitfalls – like float-time mismatch or over-packing the mold – and have tried and true protocols in place to avoid them. Let’s take a bird’s eye view look at our process:

  1. Tissue Selection: We begin by selecting high-quality tissue samples that are representative of the biological question at hand. The quality assessment is based on the spatial assay’s quality standards for RNA and morphology. Our team works closely with researchers to understand the specifics of the project, ensuring that the chosen tissues will provide the most relevant data for spatial transcriptomics analysis.

  2. Tissue Fixation and Embedding: Proper fixation and embedding are crucial for preserving tissue integrity. We utilize advanced techniques to fix tissue samples, ensuring they retain their cellular structure and molecular composition. Our embedding process ensures that tissue sections are aligned and uniformly distributed, minimizing variation and maximizing the quality of the final tissue array.

  3. Array Construction: Once the tissues are prepared, the tissue cores are carefully selected by our pathologist and/or the principal investigator. We then construct high-density tissue arrays by precisely arranging tissue cores into a compact format. This step requires expert handling to ensure that each tissue core is carefully placed to preserve spatial relationships and anatomical features.

  4. Quality Control and Validation: Quality assessment is a critical part of our tissue array construction process. At BioChain, we employ a rigorous quality control protocol, including histological analysis and staining, to ensure that tissue integrity and cellular architecture are preserved. We also verify that the tissue cores are correctly positioned within the array for optimal analysis.

  5. Customized Solutions: We understand that each research project is unique, and we offer tailored tissue array construction services to meet specific needs, for example, scan area specifications. Whether you need arrays for specialized tissue types, disease models, or specific experimental conditions, BioChain’s expert team is ready to provide customized solutions.

Integrating Tissue Quality and Reliability into Xenium TMA Construction 

In other words … Why BioChain?  

While any lab can follow Xenium’s public protocol, partnering with an experienced provider can flatten your learning curve and improve your study’s outcomes. We can promise:

  • Integrated Tissue-Quality Assessment (TQA). Pathologist-led scoring, depth checks and DV200 targeting flag weak blocks before they hit the mold.

  • Custom Size-Based Construction. Recipient blocks custom sized to Xenium’s capture window reduce trimming waste.

  • Stage-Gate QC. BioChain embeds inspection after every construction milestone, catching placement or orientation errors early.

  • Array Re-Creation on Demand. Archived blocks plus digital maps let you add new panels or replicate studies months later.
Challenge Conventional Approach BioChain Solution
Hidden tissue artifacts

Basic H&E glance

Pathologist-led Tissue Quality Assessment

Core placement bias
Manual punch-and-pray
Size-based Custom TMA design, Xenium capture window
Variable core integrity
Single QC snapshot
In-process QC at each of the five stages
Reproducibility across studies
“One-off” arrays
Archival block and metadata to recreate or expand arrays on demand

Case Study: Building Xenium’s Reference Multi-Tissue Array

Collaborating with our long-time partner 10x Genomics, BioChain constructed TMA for Xenium R&D. The 10x Genomics sample-prep team needed an FFPE block that:

  1. Held seven distinct tissues within the 8 mm capture width.

  2. Survived repeated sectioning for internal validation runs.

  3. Demonstrated consistent segmentation metrics across organs.

BioChain engineered the array by:

  • Matching float-times so fragile spleen strips weren’t displaced by denser skin.

  • Trimming each strip to 8 mm × 2 mm and aligning them in a single mold.

  • Embedding under <60 °C to preserve RNA integrity.

The finished block (pictured below) now serves as the visual benchmark for new Xenium users worldwide—a real-world proof that meticulous sampling plus disciplined construction pays dividends in data quality.

Figure 1 & 2: Sample BioChain Tissue Micro-Array for a single Xenium slide containing seven different tissues that fit in the Xenium sample area. (10x Genomics)

 

The construction of high-quality tissue arrays is a cornerstone of successful, cost effective spatial transcriptomics experiments. At BioChain, we understand the critical importance of tissue array construction and quality assessment in generating reliable, reproducible, and insightful data. Our expert team, combined with cutting-edge technology and a commitment to precision, ensures that your research is built on the strongest possible foundation.

By partnering with BioChain, researchers can unlock the full potential of spatial transcriptomics and gain deeper insights into the molecular landscape of tissues, helping to advance scientific discovery and drive progress in areas such as disease research, drug development, and personalized medicine.

Ready to rest easy about your next spatial project? Have more questions? 

Explore BioChain’s spatial-biology services or reach out with your own sampling challenge—our pathologists love a good puzzle.

Spatial is complicated. We’re here to make it simple.