Resources: Posters

Platform for Large-Scale Analysis of Brain Cell Types at Single-Cell Resolution Spanning Longitudinal Multi-Modal Measurements

November 19, 2025

Society for Neuroscience 2025

Olaia Villa, Ph.D., Assoc. Director, Collaborations

Keywords: R3200 Platform, CellCage™ technology, Neurobiology, Neural networks, Brain cell types, Longitudinal multi-modal analysis, Single-cell resolution

Keywords: R3200 Platform, CellCage™ technology, Neurobiology, Neural networks, Brain cell types, Longitudinal multi-modal analysis, Single-cell resolution

Presented by:
Olaia Villa, Ph.D., Assoc. Director, Collaborations
Presented at:
November 18, 2025

This study introduces a high-throughput workflow for the large-scale analysis of brain cell types, utilizing the R3200 Platform and CellCage™ technology. By spanning longitudinal multi-modal measurements, the research enables the precise tracking of neural networks and individual neuronal behaviors over time. The integration of advanced live-cell imaging with single-cell transcriptomics provides a comprehensive framework for studying brain function and disease states within controlled, tissue-like environments.

Case Study: Functional Profiling of Microglia in Neuroinflammation

Link microglial behavior to gene expression at single-cell resolution, for insight into neuroinflammation, drug response, and immune dysfunction in CNS disease.

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Researchers used the Cellanome R3200 to enclose individual microglia with fluorescent particles and track phagocytosis over 12 hours via fluorescent imaging. Each cell’s transcriptome was then sequenced, linking activity levels to gene expression.  

What they found: 

High-activity microglia upregulated genes in complement signaling, lipid metabolism, and lysosomal function–key pathways in neuroinflammation and repair. 

Why it matters: 

This approach overcomes key limitations in standard assays by capturing phagocytic function and gene expression in the same individual cells without dissociation, pooling, or inference. It enables a direct, scalable readout of immune heterogeneity, and reveals the transcriptional programs driving effective or impaired microglial responses.  

What’s next: 

Extend to co-cultures by layering enclosed microglia over intact neuronal networks. Study how cell-cell interactions shape phagocytic behavior and fate. Combine with cytokines, CRISPR libraries, or immunotherapies to generate time-resolved, multi-modal datasets that can be used for MoA analysis, early biomarker discovery, and AI-guided modeling in CNS disease. 

Case Study: Modeling Synapse Formation and Developmental Trajectories in 3D

Track development, function, and gene expression in intact neurospheres, a human-relevant 3D model increasingly vital as regulators move away from animal studies.

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Stem-cell-derived neurospheres offer a robust 3D model of early brain development, but standard assays disrupt their structure and miss critical dynamics.  

Approach:

Using the Cellanome R3200, the research team explored,

  • Hundreds of intact neurospheres (100–200 cells each) were cultured inside individual CellCage™ enclosures. 
  • Axon extension, synapse formation and calcium activity were tracked over multiple days. 
  • End-point RNA-Seq was linked back to each neurosphere’s functional behavior. 
  • UMAP clustering revealed lineage-specific gene programs, validated by fluorescent markers.  
What's next:

This lays the groundwork for CRISPR-based multimodal screens to probe mechanisms of development, degeneration, and repair within preserved 3D architecture. 

Why it matters:

As the FDA and others move to reduce reliance on animal models, human-relevant in vitro systems like this are increasingly essential. 

FAQ's

How does the R3200 Platform facilitate large-scale analysis of brain cells?

The R3200 Platform utilizes a highly parallel architecture that allows for the simultaneous monitoring of hundreds of individual brain cells or small neural clusters. This scalability enables researchers to conduct high-throughput studies of complex brain cell types while maintaining single-cell resolution across every sample.

What are the benefits of longitudinal multi-modal measurements in neuroscience?

Longitudinal measurements allow for the observation of dynamic neural behaviors, such as axon extension or synapse formation, as they unfold. By combining these temporal observations with end-point transcriptomics through CellCage™ technology, researchers can link specific physiological developmental trajectories to underlying genetic drivers.

How does CellCage™ technology support the study of neural networks?

CellCage™ technology provides a stable microenvironment that secures brain cells in place without traditional tissue dissociation. This preserves the structural integrity of neural networks and allows for the precise study of cell-cell interactions and long-term functional changes in a setting that more closely mimics native brain tissue.