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Differentiated cardiac organoid labeled with Fluo-4 Calcium indicator. Sample courtesy of Hyosin Paik, Yonsei University, Korea
ZEISS solutions for new approach methodologies

Organoid and 3D tissue imaging solutions for drug discovery High-resolution, scalable imaging and analysis workflows for 3D HCA imaging

Complex in vitro models (CIVMs), including organoids, spheroids, and organs-on-a-chip, require deep, gentle, and scalable 3D imaging. ZEISS microscopy systems combined with ZEISS arivis software connect image acquisition to quantitative 3D analysis for high-throughput screening and predictive drug discovery.

  • 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
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Why ZEISS for organoid imaging and 3D tissue models

ZEISS empowers biotech, pharmaceutical, and CRO teams to move confidently from 3D imaging to actionable data - improving efficiency, reducing variability, and driving predictive, reproducible results in drug discovery and development.

  • Unmatched optical performance for deep tissue and organoid imaging
  • Proven automation and stability for high-volume, high-throughput screening
  • AI-powered analytics for powerful and scalable quantification
  • Integrated end-to-end 3D imaging and analysis workflows that accelerate translational research

Advanced 3D imaging for new approach methodologies: organoids, spheroids, and organ-on-a-chip models

CIVMs 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 predictive drug discovery and personalized therapeutic development.

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 powered by advanced AI-driven analysis.

The challenge of imaging complex 3D cell cultures

Imaging complex, dense, and thick structures

Because organoids and other 3D cell cultures are thick, heterogeneous, and highly light-scattering, imaging workflows must address limitations in depth, resolution, sensitivity, speed, and throughput.

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

ZEISS Airyscan delivers super-resolution with high sensitivity

Sensitivity: Gentle Imaging – Phototoxicity damages live samples

ZEISS Lattice Lightsheet 7 and ZEISS Lightfield 4D modes minimize light exposure

Speed: High-content workflows demand faster imaging

ZEISS Celldiscoverer 7 with ZEISS LSM 910 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 well plate imaging, nuclei (DAPI), membrane (mem9-GFP), enterocytes (Aldolase B-Alexa 647).

    Intestinal organoid well plate 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: End-to-end 3D analysis and data workflows

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 Imaging paired with a powerful 3D analysis supports predictive, scalable workflows for biotech and pharma.

  • 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 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, reliable 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 and precise 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

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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, efficient segmentation and tracking for quantitative toxicology and metabolism studies

Imaging systems for new approach methodologies, including complex in vitro models (CIVMs)

  • ZEISS LSM - Confocal and Lightfield 4D

    Product photo of the ZEISS LSM 990

    From subcellular detail to dynamic 4D volumes: precision, speed, and sensitivity together in one powerful imaging portfolio. With innovations like Airyscan super-resolution, Lightfield 4D volumetric capture, and the versatile LSM 990 platform, you can image faster, deeper, and more gently than ever before. Designed for usability, reliability, and reproducibility. Turn complex live-cell dynamics into clear, quantitative insights that drive discovery forward.

    Explore the ZEISS Lightfield 4D

  • ZEISS Lattice Lightsheet 7

    Product photo of the ZEISS Lattice Lightsheet 7

    Unrivalled volumetric live-cell imaging at subcellular resolution - rapidly, gently, and reproducibly. Whether you’re observing organoids, small organisms or dynamic sub-cellular processes, the Lattice Lightsheet 7 makes advanced lattice light-sheet microscopy accessible and streamlined - enabling more insightful experiments with fewer constraints.

    Explore the ZEISS Lattice Lightsheet 7

  • ZEISS Celldiscoverer 7 with LSM

    Product photo of the ZEISS Celldiscoverer 7

    Experience a new standard in automated live-cell imaging. With intelligent optics, unmatched sensitivity, and effortless usability, Celldiscoverer 7 with LSM delivers reliable, reproducible results every time. From rapid setup to long-term, high-content experiments, it optimizes every step of your workflow - empowering you to achieve more, faster, with confidence.

    Explore the ZEISS Celldiscoverer 7

3D imaging and analysis solutions for organoid screening

ZEISS arivis Pro Software Analysis tools tailored for organoid research, including accurate 3D segmentation, quantification, and tracking of cellular dynamics
ZEISS Celldiscoverer 7 High-resolution imaging and advanced analysis capabilities that enable detailed exploration of organoid development, cellular interactions, and functional studies in real-time
ZEISS LSM Lightfield 4D Accelerate 3D Imaging and Screening of Colorectal Cancer Models for Enhanced Drug Response Analysis and Cellular Interactions
ZEISS Lightsheet 7 Explore the complexities of neuronal morphology in 3D
ZEISS LSM 990 Acquire multiple images simultaneously, reducing acquisition time and preserving sample integrity

Organoids Research FAQs

  • The thickness of organoids is often challenging for traditional confocal imaging due to light scattering, tissue absorption, and phototoxicity. ZEISS Lattice Lightsheet 7 and ZEISS Lightfield 4D provide gentle, rapid volume imaging with minimal photodamage, enabling extended time-lapse studies. The lightsheet approach illuminates only the focal plane being imaged, while lightfield offers one volume for each snapshot. The result is dramatically reduced photobleaching while maintaining exceptional image quality throughout the entire organoid volume.

    Explore the Lattice Lightsheet 7

  • High-throughput organoid screening requires limited user input combined with high-quality imaging to adequately survey each sample. The ZEISS Celldiscoverer 7 is fully automated and ensures reproducible results at scale. With its integrated workflows intended for high content screening, the Celldiscoverer 7 enables researchers to monitor development and response to treatment in either fixed or live samples.

  • This requires balancing resolution with field of view – a common challenge in organoid research. The ZEISS LSM 990 Lightfield 4D combines fast volume acquisition with enhanced sensitivity for deep confocal imaging. For comprehensive workflows, arivis Pro offers precise 3D analysis allowing you to correlate molecular-level events with tissue-scale organization patterns.