Differentiated cardiac organoid labeled with Fluo-4 Calcium indicator. Sample courtesy of Hyosin Paik, Yonsei University, Korea
ZEISS Solutions for New Approach Methodologies

Imaging solutions for complex in vitro models (CIVMs)

From depth to discovery: Scalable 3D imaging for predictive insights

Bring depth, clarity, and scalability to complex in-vitro models. ZEISS solutions for 3D tissue imaging enable deep, gentle, and reproducible visualization of spheroids, organoids, and organs-on-a-chip, unlocking predictive insights that accelerate drug discovery and development. Seamlessly integrated with the arivis analysis ecosystem, ZEISS delivers a performative workflow from imaging to quantitative interpretation, empowering researchers to transform complexity into actionable understanding.

  • Unified sample-to-insight workflow
  • High-resolution, gentle imaging for live 3D systems
  • End-to-end data management and insights, powered by AI and Copilot

Why ZEISS for 3D tissue models

ZEISS empowers Biotech, Pharma, and CROs to move confidently from 3D imaging to actionable data - improving efficiency, reducing variability, and driving more predictive insights in drug discovery and development.
  • Unmatched Optical Performance for imaging deep into complex tissues
  • Proven Automation and Stability for high-volume experiments
  • AI-Powered Analytics for scalable and reproducible quantification
  • Integrated End-to-End Workflows that accelerate translational research

Bringing depth, clarity, and scalability to 3D biology

Complex in vitro models (CIVMs) including spheroids, organoids, and organs-on-a-chip are reshaping how the pharmaceutical and biotechnology industries study disease, evaluate drug efficacy and safety, and develop new therapies. By more closely replicating the structure and function of human tissues compared to traditional 2D cultures, these advanced 3D systems deliver greater translational relevance, reduce reliance on animal testing, and accelerate the development of more predictive and personalized medicine.

As adoption of 3D systems accelerates across pharma, biotech, and CROs, new challenges have emerged: thick, scattering, and heterogeneous samples require imaging systems that combine depth, sensitivity, resolution, and throughput, while handling the massive datasets generated in volumetric studies.

ZEISS 3D Imaging Solutions, integrated with ZEISS arivis ecosystem, deliver a unified workflow for 3D tissue imaging and analysis, enabling deep, gentle imaging, and reproducible results that scale from single organoids to plate-based screening, supported by Copilot-guided acquisition and powerful 3D segmentation algorithms including superior AI tools.

The challenge

Imaging complex, dense, and thick structures

3D cell cultures present a unique set of technical barriers that can limit insight and reproducibility. ZEISS addresses all five major imaging and analysis challenges faced in this field:

Challenge

How we address it

Penetration Depth: Scattering and refractive mismatches limit light penetration

Advanced optics and confocal and lightsheet modalities optimize depth without compromising resolution

Resolution: Small subcellular details are lost in thick samples

Airyscan delivers super-resolution with high sensitivity

Sensitivity: Gentle Imaging – Phototoxicity damages live samples

Lattice Lightsheet 7 and Lightfield 4D modes minimize light exposure

Speed: High-content workflows demand faster imaging

Celldiscoverer 7 with Lightfield 4D module ensures rapid volumetric acquisition

Throughput: Drug discovery requires scalability

Integrated automation and ZEISS arivis analytics enable plate-based, high-volume workflows with 3D context and a multitude of 3D parameters

  • 35 day old neuronal organoids. Sample courtesy of: Daniel Reumann and Jürgen Knoblich, Institute of Molecular Biotechnology (IMBA) of the Austrian Academy of Sciences
  • Intestinal organoid wellplate imaging, nuclei (DAPI), membrane (mem9-GFP), enterocytes (Aldolase B-Alexa 647).
  • 3D Organoid, sub cellular structures (Epithelial Cell Layer and Inner Lumen). Study the role of Wnt signaling in organoid formation.
  • 35 day old neuronal organoids. Sample courtesy of: Daniel Reumann and Jürgen Knoblich, Institute of Molecular Biotechnology (IMBA) of the Austrian Academy of Sciences
  • 35 day old neuronal organoids. Sample courtesy of: Daniel Reumann and Jürgen Knoblich, Institute of Molecular Biotechnology (IMBA) of the Austrian Academy of Sciences
  • Intestinal organoid wellplate imaging, nuclei (DAPI), membrane (mem9-GFP), enterocytes (Aldolase B-Alexa 647).
    Intestinal organoid wellplate imaging, nuclei (DAPI), membrane (mem9-GFP), enterocytes (Aldolase B-Alexa 647).

    Intestinal organoid wellplate imaging, nuclei (DAPI), membrane (mem9-GFP), enterocytes (Aldolase B-Alexa 647).

    Intestinal organoid wellplate imaging, nuclei (DAPI), membrane (mem9-GFP), enterocytes (Aldolase B-Alexa 647).

  • 3D Organoid, sub cellular structures (Epithelial Cell Layer and Inner Lumen). Study the role of Wnt signaling in organoid formation.
    3D Organoid, sub cellular structures (Epithelial Cell Layer and Inner Lumen). Study the role of Wnt signaling in organoid formation.

    3D Organoid, sub cellular structures (Epithelial Cell Layer and Inner Lumen). Study the role of Wnt signaling in organoid formation.

    3D Organoid, sub cellular structures (Epithelial Cell Layer and Inner Lumen). Study the role of Wnt signaling in organoid formation.

  • 35 day old neuronal organoids. Sample courtesy of: Daniel Reumann and Jürgen Knoblich, Institute of Molecular Biotechnology (IMBA) of the Austrian Academy of Sciences
    35 day old neuronal organoids. Sample courtesy of: Daniel Reumann and Jürgen Knoblich, Institute of Molecular Biotechnology (IMBA) of the Austrian Academy of Sciences

    35 day old neuronal organoids. Sample courtesy of: Daniel Reumann and Jürgen Knoblich, Institute of Molecular Biotechnology (IMBA) of the Austrian Academy of Sciences

    35 day old neuronal organoids. Sample courtesy of: Daniel Reumann and Jürgen Knoblich, Institute of Molecular Biotechnology (IMBA) of the Austrian Academy of Sciences

Beyond imaging

Simplifying acquisition to insight with ZEISS arivis

Modern imaging technologies reveal the intricate complexity of biological systems, but true understanding comes from turning data into knowledge. ZEISS arivis extends the power of ZEISS imaging platforms by streamlining the entire 3D data journey, transforming high-content images into reproducible, shareable, and scalable insights.

Through the integration of AI-driven analysis, efficient data management, and cloud-based collaboration, researchers can move seamlessly from image acquisition to interpretation and decision-making.

This unified ecosystem enables consistent workflows, accelerates discovery, and supports scalable infrastructure for both academic and industrial research environments.  

Highlights

This synergy enables predictive, reproducible, and scalable imaging for biotech and pharma innovation
  • AI-Driven 3D Segmentation

    Automated, accurate object recognition even in noisy or heterogeneous samples.

  • Efficient Data Handling

    Work effortlessly with terabyte-scale datasets on standard hardware.

  • Scalable Cloud Analysis

    Collaborate globally and scale projects without infrastructure limits.

  • Reproducible Quantification

    Standardize pipelines for consistent, comparable results across studies.

  • Integrated Workflow

    Combine imaging, analysis, and automation for predictive, reproducible outcomes.

  • Copilot-Guided, AI-Powered Workflows

    From acquisition to analysis, AI and Copilot accelerate setup, execution, and reproducibility.

ZEISS arivis software has allowed us to extract crucial insights from our high-content imaging experiments, leading to better-informed decisions in drug discovery and development.

Marta da Silva, PhD Senior Scientist, Charles River Laboratories

Application focus

Proven workflows for complex 3D Systems
Human breast cancer organoids. 3D rendering with arivis. Image courtesy of S. Gawrzak and M. Jechlinger, EMBL, Heidelberg, Germany

Human breast cancer organoids. 3D rendering with arivis. Image courtesy of S. Gawrzak and M. Jechlinger, EMBL, Heidelberg, Germany

S. Gawrzak and M. Jechlinger, EMBL, Heidelberg, Germany

Human breast cancer organoids. 3D rendering with arivis. Image courtesy of S. Gawrzak and M. Jechlinger, EMBL, Heidelberg, Germany

Human breast cancer organoids in matrigel

Solution: ZEISS Celldiscoverer 7 with LSM / Airyscan + ZEISS arivis

Key outcomes:

  • Deep, high-resolution imaging through scattering matrices
  • Gentle long-term acquisition of live tumor organoids
  • High-throughput image capture and analysis across multiwell plates
  • AI-powered segmentation for rapid, reproducible quantification
Human Embryonic Stem Cell-Derived Spinal Cord Organoids in cell culture media and Matrigel. EGFP-tagged tight junctions. Image courtesy of G. Anand, Ramanathan Lab, Harvard University, Cambridge, US

Human Embryonic Stem Cell-Derived Spinal Cord Organoids in cell culture media and Matrigel. EGFP-tagged tight junctions. Image courtesy of G. Anand, Ramanathan Lab, Harvard University, Cambridge, US

G. Anand, Ramanathan Lab, Harvard University, Cambridge, US

Human Embryonic Stem Cell-Derived Spinal Cord Organoids in cell culture media and Matrigel. EGFP-tagged tight junctions. Image courtesy of G. Anand, Ramanathan Lab, Harvard University, Cambridge, US

Human embryonic stem cell-derived spinal cord organoids

Solution: ZEISS Lattice Lightsheet 7 + ZEISS arivis

Key outcomes:

  • Fast, gentle, high-resolution imaging of developing organoids
  • Phototoxicity-free visualization of real-time tissue dynamics
  • Seamless cloud-based analysis and data sharing for multi-sample studies
  • Scalable handling of large datasets with ZEISS arivis  
Cleared spheroid of a coculture of HCT-116-GFP (colon cancer) / NIH-3T3-RFP (fibroblasts) cells stained with Hoechst for nuclei. Imaged in an InSphero Akura plate. Dataset was segmented using arivis Pro. Sample courtesy of InSphero AG. Schlieren, Switzerland

Cleared spheroid of a co-culture of HCT-116-GFP (colon cancer)

Solution: ZEISS LSM 910/990 with Lightfield 4D + ZEISS arivis

Key outcomes:

  • Deep and fast imaging
  • High sensitivity for short exposure times
  • High-throughput acquisition of numerous Spheroids in multiwell plates
  • Scalable 4D analysis and efficient segmentation for quantitative toxicology and metabolism studies

Imaging systems for complex in vitro models (CIVMs)

Organoids Research FAQs

  • Organoids often exceed 200-500μm in thickness, making traditional confocal imaging challenging due to light scattering and phototoxicity concerns. ZEISS Lightsheet 7 and Lattice Lightsheet 7 systems provide gentle, rapid volume imaging with minimal photodamage, enabling extended time-lapse studies. The lightsheet approach illuminates only the focal plane being imaged, dramatically reducing photobleaching while maintaining exceptional image quality throughout the entire organoid volume.

  • ZEISS microscopes such as Celldiscoverer 7 and LSM 990 with Airyscan offer environmental control (CO₂, humidity, temperature) and sensitive detectors to ensure high-quality imaging with minimal phototoxicity, enabling researchers to monitor development and response to treatment in real time.

  • This requires balancing resolution with field of view - a common challenge in organoid research. The ZEISS LSM 990 Lightfield 4D provides enhanced sensitivity for deep confocal imaging, while Lattice SIM 3 offers super-resolution capabilities when subcellular detail is critical. For comprehensive workflows, arivis Pro enables seamless integration of multi-scale datasets, allowing you to correlate molecular-level events with tissue-scale organization patterns.

  • Core facilities need versatile platforms that can support everything from basic morphology to advanced live-cell imaging. ZEISS systems offer modular configurations - the LSM 990 can be equipped for routine organoid imaging and upgraded for specialized applications, while the Celldiscoverer 7 serves both screening and detailed analysis needs. arivis Pro provides consistent analysis workflows across different imaging modalities, reducing training overhead and ensuring reproducible results regardless of which system users choose..

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