Building a Morphology Core for Tumor Microenvironment Research at the Chinese Academy of Sciences

Advancing Tumor Microenvironment Research with Digital Pathology

At the Chinese Academy of Sciences (CAS), the Morphology Core serves as a shared research platform. It transforms tissue samples into consistent, quantitative digital data. As a result, researchers can support both basic research and translational studies with greater efficiency and confidence.

Like many leading research institutes, the core faces two major challenges. First, it processes hundreds of brightfield slides every day for routine histology, validation, and long-term archiving. At the same time, researchers increasingly rely on TSA-based multiplex immunofluorescence (mIF) to study the tumor microenvironment (TME) at scale.

To meet both demands, the Morphology Core adopted the KFBIO Digital Pathology Platform. This integrated whole-slide imaging (WSI) solution combines brightfield and fluorescence imaging within a single workflow. Consequently, researchers can standardize image acquisition while improving efficiency across multiple projects.

The platform supports:

• TSA multiplex immunofluorescence (mIF) for tumor microenvironment (TME) profiling
• Ultra-fast brightfield whole-slide scanning for routine pathology workflows
• Large-scale digital archiving and dataset generation for computational pathology and AI research

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Scientific Background: Why TLS Matters in Tumor Microenvironment Research

Understanding the Role of Tertiary Lymphoid Structures

Tertiary lymphoid structures (TLSs) develop at sites of chronic inflammation, including many solid tumors. These organized immune cell clusters mainly contain B cells, T cells, and dendritic cells. Today, TLSs are recognized as valuable biomarkers in cancer research.

Studies have shown that TLSs can help predict overall survival in untreated cancer patients. In addition, they are closely associated with responses to immunotherapy in many solid tumors. Therefore, TLS assessment has become an important part of tumor microenvironment (TME) research.

Why Traditional TLS Assessment Is Challenging

Despite their growing importance, evaluating TLSs remains difficult. Traditional microscopy is time-consuming and often depends on additional tissue sections stained with immunohistochemistry (IHC) or immunofluorescence.

For a morphology core supporting multiple research teams, this approach creates several limitations. Researchers need a workflow that delivers reliable TLS assessment while maintaining high throughput. Equally important, the workflow should generate standardized digital data that can be reanalyzed, shared across projects, and used for high-quality scientific publication

The Challenge: From Manual Review to Standardized Digital Pathology Data

Meeting the Needs of Modern Research

As more research teams adopted digital pathology, the Morphology Core faced several common challenges. Traditional microscopy could no longer support the growing number of projects. Therefore, the core needed a faster, more standardized workflow that could deliver reliable and shareable data.

1. Increasing Throughput

Manual microscopy cannot keep pace with today’s high-volume tissue workflows. As the number of slides continues to grow, digital scanning must become the standard rather than the exception.

Fast whole-slide imaging (WSI) is essential for routine histology, quality control, remote review, and long-term data management.

2. Supporting Flexible Multiplex Immunofluorescence

TSA multiplex immunofluorescence panels continue to evolve. Researchers frequently update antibodies, fluorophores, and channel combinations. Therefore, the imaging platform must remain compatible with commonly used TSA dyes while supporting future expansion.

An open platform also gives research teams greater flexibility when designing new experiments.

3. Detecting Weak Fluorescence Signals

Many tumor microenvironment (TME) studies rely on weak or sparsely distributed biomarkers. Consequently, researchers need stable illumination, high-quality optical filters, and sensitive image detection.

Reliable fluorescence imaging is especially important when comparing different batches, research groups, or clinical cohorts.

4. Turning Images into Quantitative Results

Capturing high-quality images is only the first step. Researchers also need tools for cell segmentation, co-localization analysis, intensity measurement, and spatial analysis.

Together, these capabilities transform digital slides into reproducible, quantitative research results that support scientific publication and collaboration.

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The KFBIO Solution: An Integrated Digital Pathology Platform

From Image Acquisition to Quantitative Analysis

Instead of using a standalone scanner, the CAS Morphology Core adopted the KFBIO Digital Pathology Platform as a complete workflow solution.

The platform connects every stage of digital pathology:

Sample Preparation → Staining → Whole-Slide Scanning → Image Analysis → Research Output

As a result, researchers can standardize data generation while improving workflow efficiency and reproducibility across multiple projects.

1. High-Speed Brightfield Whole-Slide Imaging

The platform uses advanced line-scan technology to maximize scanning efficiency.

Scanning performance includes:

• 15 × 15 mm slides at 20× in as little as 15 seconds
• 40× scanning in as little as 40 seconds

This high-speed performance supports:

• Routine H&E digitization
• IHC slide scanning
• High-throughput digital archiving
• Remote pathology review
• Centralized quality control
• AI training dataset generation

Consequently, laboratories can digitize routine pathology slides without slowing daily operations.

2. Flexible TSA Multiplex Fluorescence Imaging

The platform supports up to 10 customizable fluorescence channels for whole-slide imaging.

Researchers can configure channel combinations to match different experimental designs. Moreover, the system remains flexible as future multiplex panels become more complex.

Configurable full-band LED excitation also allows users to adjust spectral settings independently. As a result, researchers can balance fluorescence intensity with dye stability across different fluorophores.

3. High-Efficiency Optical Filters for Accurate Quantification

Accurate multiplex analysis depends on clean spectral separation. Therefore, the platform incorporates high-performance optical components designed for quantitative fluorescence imaging.

Key features include:

• Chroma filter sets
• Support for customized multi-pass filters
• Up to 99% light transmission with OD6 blocking

These features reduce spectral bleed-through and improve image contrast. Consequently, researchers can achieve more reliable quantitative results across multiplex fluorescence experiments.

4. Sensitive sCMOS Detection for Dim Biomarkers

Detecting weak fluorescence signals is essential for tumor microenvironment research.

The platform uses a scientific sCMOS camera that provides:

• Spectral response from 180–1100 nm
• Up to 95% quantum efficiency at 560 nm

This sensitive detection improves visualization of dim TLS- and TME-related biomarkers. As a result, researchers can collect higher-quality imaging data with greater confidence.

5. Precise Channel Alignment for Reliable Spatial Analysis

Accurate Multi-Channel Registration

Accurate channel alignment is essential for multiplex immunofluorescence (mIF). Even small registration errors can affect co-localization analysis and lead to inaccurate biological interpretation.

To ensure reliable results, the KFBIO Digital Pathology Platform delivers highly repeatable image registration across multiple fluorescence channels.

Key performance features include:

• Positioning resolution down to 20 nm
• Multi-channel alignment controlled to within one pixel

As a result, researchers can perform spatial analysis and co-expression studies with greater confidence. More importantly, the generated data accurately reflects biological characteristics rather than imaging artifacts.

6. Open Data Export for Flexible Research Workflows

Integrating with Existing Analysis Platforms

Research teams often use different image analysis software and AI platforms. Therefore, compatibility is essential for collaborative research.

The KFBIO platform supports export in widely used digital pathology formats, making it easy to integrate with existing workflows.

Supported formats include:

Brightfield

• KFB
• TIF
• SVS
• DICOM (DCM)

Fluorescence

• KFBF
• QPTIFF

Because of this open design, researchers can analyze images using their preferred software. They can also share datasets across institutions without changing their existing workflow. Consequently, collaboration becomes faster and more efficient.

Workflow in Practice: Standardized TLS Analysis with TSA Multiplex Immunofluorescence

A Reproducible Digital Pathology Workflow

The CAS Morphology Core follows a standardized workflow for tumor microenvironment (TME) studies. Each step helps improve data quality, workflow efficiency, and research consistency.

Step 1. Design the TSA Multiplex Panel

Researchers first design a multiplex panel based on the study objectives. They then stain tissue sections to identify B cells, T cells, antigen-presenting cells (APCs), and other immune cell populations within tumor and stromal regions.

Step 2. Acquire Whole-Slide Fluorescence Images

Next, slides are scanned using optimized fluorescence channel settings. Efficient optical filters and sensitive image detection help capture clear, high-quality signals across all markers.

Step 3. Perform Quality Control

After image acquisition, the system automatically verifies channel alignment and image quality. Pixel-level registration ensures that spatial relationships accurately represent biological structures.

Step 4. Quantify and Analyze Spatial Information

Finally, researchers perform:

• Cell segmentation
• Co-localization analysis
• Fluorescence intensity measurement
• Spatial distribution analysis

Together, these analyses convert digital pathology images into standardized and comparable quantitative data. This information supports cross-project research, scientific publication, and AI model development.

Why This Matters for Modern Morphology Cores

Modern morphology cores need more than fast slide scanning. They also need standardized digital workflows that produce reliable, reusable research data.

By combining ultra-fast brightfield whole-slide imaging with flexible multiplex immunofluorescence, the KFBIO Digital Pathology Platform supports both routine pathology work and advanced tumor microenvironment research.

In addition, researchers can standardize image acquisition, improve workflow efficiency, and simplify collaboration across multiple laboratories. These advantages help morphology cores manage increasing workloads while maintaining consistent data quality.

Most importantly, every digital slide becomes a reusable research asset. Teams can review, reanalyze, and share data whenever new scientific questions arise. As a result, research becomes more reproducible, collaborative, and scalable.

Conclusion

As digital pathology continues to transform biomedical research, morphology cores require solutions that support both routine operations and advanced spatial biology studies.

The KFBIO Digital Pathology Platform provides an end-to-end workflow that combines high-speed whole-slide imaging, flexible multiplex immunofluorescence, sensitive fluorescence detection, and quantitative image analysis within a single platform.

Whether supporting large-scale digital archiving, tumor microenvironment research, TLS evaluation, or AI-assisted pathology, the platform helps research institutions generate standardized, high-quality data with greater efficiency.

Ultimately, the Chinese Academy of Sciences Morphology Core demonstrates how an integrated digital pathology solution can accelerate scientific discovery while creating reproducible data that researchers can trust today and build upon in the future.

KF-FL-005 KF-FL-020 KF-FL-120 KF-FL-400