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Cell model architectures for organoids, spheroids, and 3D assays

RASTRUM™ and RASTRUM™ Allegro offer a library of 3D cell model architectures designed to match different experimental needs, from imaging and drug screening to migration, invasion, histology, omics, and intact model recovery.
The right architecture depends on what you need to model, measure, image, recover, or scale. Use this page to identify the physical 3D model configuration that best fits your experiment.
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Choose the architecture around your experimental question

There is no one-size-fits-all 3D model architecture. A format optimized for fast imaging may not generate enough material for RNA, protein, or flow cytometry. A model designed for high-throughput screening may not be the best choice for histology, spatial transcriptomics, or intact model recovery.

RASTRUM Cell Model Architectures help researchers control how cell-loaded matrices are placed within each well, enabling different experimental designs across 96-well, 384-well, and 24-well plate formats.

Architecture choice should consider:

  • Whether you are working with spheroids, organoids, tumoroids, co-cultures, or cell aggregates
  • Whether the study requires imaging, high content screening, molecular analysis, flow cytometry, histology, or model recovery
  • Whether the model should use a single matrix region, adjacent matrix regions, a triple-matrix interface, or a transwell insert membrane format
  • Whether the experiment requires migration, invasion, paracrine signaling, neurite outgrowth, or wound healing assay workflows
  • Whether the workflow needs to scale into 384-well plate screening 

Why the Inert Base matters

 Most RASTRUM architectures include an Inert Base, a non-functionalized PEG-based gel layer printed between the 3D model and the well surface. This helps prevent cells from migrating out of the 3D gel and forming a 2D monolayer on the plastic underneath, which can introduce non-3D cell behavior into the experiment. 

 

Organoids vs Spheroids: Why architecture matters

Organoids and spheroids are both used in 3D cell culture, but they are not the same model type, and they may require different architecture choices depending on the experiment.

Organoids are often more complex 3D structures that may represent aspects of tissue organization, differentiation, or patient-derived biology, depending on the cell source and culture conditions. They may require architectures that support expansion, imaging, histological processing, spatial transcriptomics compatibility, or downstream molecular analysis.

Spheroids are typically 3D cell aggregates that are relatively easy to generate and scale, making them useful for screening, treatment-response studies, cytotoxicity assays, and scalable 384-well plate workflows. Because they are simpler aggregate models, spheroids generally do not capture tissue organization or architecture to the same extent as organoids and are often used for single-cell-type response studies or simpler co-culture experiments.

RASTRUM architectures can support different organoid, spheroid, and tumoroid workflows depending on the required plate format, matrix environment, model size, imaging needs, recovery needs, and downstream analysis.

For example:

  • Use Imaging when fast brightfield or immunofluorescence imaging is the priority.
  • Use Large Plug or Large Plug V2 when more cellular material is needed for DNA, RNA, protein, omics, or flow cytometry.
  • Use Immunohistochemistry or Removable when intact model handling, histology, spatial transcriptomics, or spatial biology workflows are needed downstream.
  • Use Screening or High Throughput when scaling drug response or cytotoxicity assays into 384-well plate formats.
 

Architecture chooser

Use this as a starting point before reviewing the full architecture descriptions below.

Experimental need

Recommended starting architecture family

Fast imaging with minimal cell usage

Imaging models

DNA, RNA, protein, omics, or flow cytometry analysis

Large Plug models

384-well drug screening, cytotoxicity assays, high content screening, or assay development

Screening and high-throughput models

Spatially defined co-culture, migration, invasion, neurite outgrowth, gap closure, or wound healing assay workflows

Dual and Triple Matrix models

Transwell migration assay, chemotaxis, or paracrine signaling

Mematix models

Histology, immunohistochemistry, spatial transcriptomics compatibility, spatial biology workflows, sectioning, or intact model recovery

Removable models

RASTRUM Cell Model Architectures

Unless otherwise noted, RASTRUM architectures are compatible with brightfield imaging, immunofluorescence imaging, and biochemical downstream analysis platforms. Unless otherwise noted, each architecture is available on both RASTRUM and RASTRUM Allegro.

Imaging models for brightfield and immunofluorescence imaging

Use Imaging models when image-based analysis is the primary readout and cell input needs to stay low. The Imaging architecture is a small single-matrix format designed for brightfield and immunofluorescence imaging in 96-well workflows.

Architectures included: Imaging

Compatibility: 96-well plates on RASTRUM and RASTRUM Allegro.

Best for

  • Brightfield imaging
  • Immunofluorescence imaging
  • Drug screening and biochemical assays where image-based analysis is the main readout
  • Organoid, spheroid, tumoroid, or direct co-culture imaging
  • Automated imaging and high content microscopy workflows where compatible

 

Key points

  • Small model footprint for efficient imaging
  • Lower cell usage than larger architectures
  • Useful when the model will primarily be assessed in place by imaging

Large Plug models for DNA, RNA, protein, and omics analysis

Use Large Plug models when the experiment needs more cellular material for molecular or cell-based downstream analysis. This group includes the standard Large Plug architecture and Large Plug V2 for RASTRUM Allegro workflows.

Architectures included: Large Plug and Large Plug V2

Compatibility: Large Plug supports 96-well workflows on RASTRUM. Large Plug V2 supports 96-well workflows on RASTRUM Allegro.

Best for

  • DNA analysis
  • RNA analysis
  • Protein analysis
  • Flow cytometry
  • Omics workflows
  • PCR, RNA-seq, Western blot, mass spectrometry, proteomics, and related workflows

 

Key points

  • Larger matrix format for increased cellular material
  • Better suited to molecular and cell recovery workflows than small imaging formats
  • Large Plug V2 should be described as the RASTRUM Allegro version of the same use case, not as a separate public-facing category

Screening and high-throughput models for 384-well drug screening and cytotoxicity assays

Use Screening and high-throughput models when scaling 3D models into 384-well screening workflows. Screening is the RASTRUM Allegro architecture for 384-well screening workflows. High Throughput supports comparable 384-well workflows on RASTRUM.

Architectures included: Screening and High Throughput

Compatibility: Screening supports 384-well workflows on RASTRUM Allegro. High Throughput supports 384-well workflows on RASTRUM.

Best for

  • 384-well drug screening
  • Cytotoxicity assays
  • Mechanistic studies
  • High content screening and high-content imaging where compatible
  • Biochemical assays and compatible colorimetric assays

 

Key points

  • Groups the two closely related 384-well architectures into one customer-facing section
  • Leads with the RASTRUM Allegro Screening architecture, per Susan approval
  • Avoids making customers compare two similar-sounding 384-well sections

Dual and Triple Matrix models for spatially defined co-culture, migration, and invasion

Use Dual and Triple Matrix models when spatial relationships between cell populations or matrix compartments are central to the study. These architectures support adjacent or multiple defined matrix regions for studying interaction, movement, and crosstalk.

Architectures included: Dual-Matrix, Triple Matrix - Imaging, and Triple Matrix - Large Plug

Compatibility: 96-well plates on RASTRUM and RASTRUM Allegro.

Best for

  • Spatially defined co-culture
  • Migration and invasion studies
  • Invasion assay workflows
  • Cell-cell communication and tissue-interface studies
  • Neurite outgrowth
  • Immuno-oncology, metastasis, gap closure, and wound healing assay workflows

 

Key points

  • Supports controlled placement of cell populations or matrix compartments
  • Configuration can be selected based on distance between compartments, model size, imaging needs, and downstream analysis
  • Avoid describing cells as layered. Use defined compartments, adjacent regions, interfaces, or triple-matrix formats instead

Mematix models for transwell migration and paracrine signaling

Use Mematix when the experiment needs a transwell insert membrane format for migration, chemotaxis, or paracrine signaling between separated compartments.

Architectures included: Mematix

Compatibility: 96-well plates on RASTRUM and RASTRUM Allegro.

Best for

  • Transwell migration assay workflows
  • Chemotaxis
  • Evaluation of cell movement and migration
  • Paracrine signaling studies
  • Invasion studies where a membrane-based design is required

 

Key points

  • Designed for transwell insert membrane workflows
  • Supports separated media chambers and chemoattractant gradients
  • Distinct enough to remain its own public-facing section

 

Removable models for histology, immunohistochemistry, and spatial workflows

Use Removable models when the intact 3D model needs to be handled outside the well for downstream histology or spatial workflows. This grouped section covers both Removable and Immunohistochemistry architecture options without presenting Immunohistochemistry as a standalone visual section.

Architectures included: Removable and Immunohistochemistry

Compatibility: 24-well plates on RASTRUM and RASTRUM Allegro.

Best for

  • Histology
  • Immunohistochemistry and H&E staining
  • Sectioning, embedding, and intact model recovery
  • High-resolution fluorescence or brightfield microscopy
  • Spatial transcriptomics compatibility and spatial biology workflows performed downstream by the customer or partner lab
  • Implantation into mouse models for preclinical research, only if approved for public web copy

 

Key points

  • Keeps immunohistochemistry and spatial workflows visible without using a misleading standalone IHC image
  • RASTRUM does not perform spatial transcriptomics or spatial biology analysis. This section should be framed as compatibility with downstream workflows
  • If an approved true IHC or H&E image becomes available later, it can replace the current lead visual

How architecture choice fits with matrix choice

Architecture controls the physical arrangement of the model in the well. Matrix controls the biochemical and mechanical environment around the cells.

Both choices matter.

For example, a researcher studying invasion may need a Dual-Matrix or Triple Matrix architecture to define where different cell populations are placed. That same researcher may also need a matrix with stiffness, adhesion cues, or remodeling properties appropriate for the biology being studied.

Use the architecture to define the model layout. Use the matrix to define the cell environment.

How it works

RASTRUM helps researchers build 3D cell models by combining matrix selection, architecture selection, cell preparation, automated printing, and downstream analysis planning.

 

Select your matrix

Choose a defined, tunable matrix based on the biological question, cell type, stiffness needs, ECM cues, remodeling requirements, and downstream analysis plan.

Choose the cell model architecture

Select the physical configuration that fits your experiment, whether you need imaging, screening, co-culture, migration, invasion, immunohistochemistry, spatial transcriptomics compatibility, model recovery, or bulk molecular analysis.

Prepare your cells

Prepare selected cells for printing, including cell lines, primary cells, patient-derived cells, iPSC-derived cells, spheroids, organoids, tumoroids, or co-culture systems depending on the study design.

Generate 3D cell models

Use RASTRUM technology to print cell-loaded matrices into the selected architecture and plate format.

Perform downstream analysis

Grow, treat, image, recover, section, stain, or analyze models using downstream workflows aligned to the architecture and research question.
Step-by-step process for generating 3D cell models with RASTRUM Allegro: select matrix, choose architecture, prepare cells, print models, and perform downstream analysis for high-throughput drug discovery and biomedical research.
FAQs
What are RASTRUM cell model architectures?

RASTRUM cell model architectures are predefined 3D model formats that control how cell-loaded matrices are arranged within a well. Different architectures support different experimental goals, such as imaging, screening, co-culture, migration, invasion, histology, or molecular analysis.

What is an inert base layer, and why does RASTRUM use one?

An inert base layer is a non-functionalized PEG-based gel layer printed between the tissue culture plastic and the 3D cell model. Most RASTRUM architectures include this layer to help prevent cells from attaching to the bottom of the well and forming a 2D monolayer, which can introduce non-3D cell behavior into the experiment.

How do I choose the right RASTRUM architecture family?

Start with the experimental goal, plate format, available cell input, and downstream analysis plan. Imaging-focused studies may use Imaging models. Molecular analysis may require Large Plug models. Screening workflows may use Screening and high-throughput models. Migration, invasion, and spatially defined co-culture studies may use Dual and Triple Matrix models or Mematix. Histology or intact model recovery may require Removable models.

What is the difference between a spheroid and an organoid?

A spheroid is typically a 3D aggregate of cells used to study cell-cell interaction, growth, viability, drug response, and cytotoxicity assays. An organoid is generally a more complex 3D model that may better represent aspects of tissue organization, differentiation, or patient-derived biology depending on the cell source and culture conditions.

Which RASTRUM architecture family is best for organoids or tumoroids?

The best architecture family depends on the readout, model size, and downstream analysis plan. Imaging models may be useful when image-based analysis is the priority. Large Plug models may be better when more material is needed for DNA, RNA, protein, omics, or flow cytometry. Removable models may be appropriate when intact model handling, histology, or spatial workflow compatibility is required.

Which architecture family supports immunohistochemistry or spatial transcriptomics?

Removable models support intact model handling for downstream histology, immunohistochemistry, spatial transcriptomics compatibility, and spatial biology workflows. RASTRUM does not perform the downstream spatial analysis. These architectures are designed to support model preparation and recovery for workflows performed by the customer or partner lab.

Which architecture family should I use for migration, invasion, or paracrine signaling?

Dual and Triple Matrix models and Mematix support different migration and invasion study designs. Mematix is suited to transwell migration assay, chemotaxis, and paracrine signaling workflows. Dual and Triple Matrix models are suited to spatially defined co-culture, tissue interfaces, invasion assay workflows, gap closure, neurite outgrowth, and wound healing assay workflows.

Which architecture family is used for 384-well screening?

Use Screening on RASTRUM Allegro or High Throughput on RASTRUM. Both belong to the Screening and high-throughput family and support scalable 384-well workflows for drug screening, cytotoxicity assays, and related assay-development work.

Which architecture family is best for DNA, RNA, protein, and omics analysis?

Large Plug models are generally better suited to DNA, RNA, protein, omics, flow cytometry, and related molecular analysis workflows because they provide more cellular material than smaller imaging-focused formats. Large Plug V2 serves a similar purpose for RASTRUM Allegro workflows.

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