3D InSight™ | 3D In Vitro Gastrointestinal Toxicology
Drug-Induced Gastrointestinal Toxicity (DIGIT) is a major driver of dose-limiting adverse events, imposing significant patient burden and contributing to treatment discontinuation and clinical attrition. Despite its clinical importance, early predictive assessment of gastrointestinal (GI) risk remains limited.
Conventional 2D in vitro models lack the structural and cellular complexity required to reliably capture gastrointestinal liabilities. As a result, GI safety risks are often identified only in later stages of drug development, when mitigation options are constrained. Advancing scalable, human-relevant in vitro models is essential to enable earlier, more confident gastrointestinal safety decisions.
Industry-Ready Early Gastrointestinal Toxicity Prediction with Patient-Derived Human Intestinal Organoids
We offer a standardized, high-throughput Drug-Induced Gastrointestinal Toxicity (DIGIT) screening platform designed for early, reliable GI risk prediction designed for therapeutic drug discovery pipelines.
By combining patient-derived human intestinal organoids with automated phenotypic imaging on the scalable Gri3D® technology, we generate physiologically relevant, quantitative, and reproducible safety data. The platform enables the detection of dose-dependent cytotoxicity in small intestinal organoids and the functional assessment of drug-induced risks of fluid secretion.
Built for routine discovery screening across diverse therapeutic modalities, our established workflow delivers fast turnaround, cost-efficient scalability, and robust, decision-ready datasets to enable confident go/no-go decisions early in drug development.
Why Gastrointestinal Toxicity Screening with InSphero
Human-Relevant Intestinal Organoids
Predict GI liabilities in patient-derived organoids that recapitulate native epithelial structure and cellular complexity, increasing translational confidence.
Established Workflows with Fast Turnaround
Rely on standardized, routine workflows delivering reliable results with fast turnaround times aligned to early discovery needs.
Scalable Screening Capacity
Evaluate larger drug sets efficiently using Gri3D® technology and automated phenotypic imaging, without compromising physiological
relevance.
Actionable, Decision-Ready Data
Receive robust, quantitative IC₅₀ values and functional insights, enabling confident cytotoxicity assessments for early go/no-go decisions with single organoid resolution.relevance.
Your Trusted Partner for Predictive Intestinal Toxicity Testing
Building on more than 16 years of expertise in delivering scalable, predictive DILI screening, we now extend our capabilities to industry-ready gastrointestinal toxicity assessment using patient-derived human intestinal organoids.
Our platform enables early, reliable evaluation of GI cytotoxicity liabilities, helping you accelerate lead optimization and advance safer drug candidates with greater confidence.
Reliable Intestinal Toxicity Prediction with “Mini-Gut” Organoids
Enable human-relevant GI safety decisions with patient-derived gastrointestinal organoids. These physiologically relevant 3D models replicate key epithelial cell populations and preserve functional activity and barrier integrity, supporting predictive detection of drug-induced intestinal liabilities with strong translational relevance.
Harnessing Gri3D® plates, the platform delivers reproducible, scalable, high-quality data to support early go/no-go decisions during the drug discovery pipeline.
Figure: Patient-derived human small intestine organoid cultured in Gri3D® plates, comprising key epithelial cell types, recapitulating mini-gut architecture in a scalable 3D format for GI cytotoxicity screening.
Data-Driven Go/No-Go Decisions with Automated Phenotypic Imaging
Predict gastrointestinal toxicity risk with confidence using our high-throughput cytotoxicity assay based on patient-derived small intestinal organoids. Assess multiple concentrations across biological replicates and clinically relevant exposure windows to generate robust, quantitative dose-response data.
Combined assessment of organoid morphology and viability, together with automated imaging of live/death staining at single-organoid resolution, delivers reliable IC₅₀ values. The statistical power of >70 organoids per well enables clear, actionable insights.
Discover our peer-reviewed high-throughput automated organoid culture
method: Brandenberg et al.,2020
Figure: Calcein AM/Ethidium homodimer Live/death staining at single-organoid level after drug (colchicine) treatment. Boxplots showing cytotoxicity ratio (EthD1 mean intensity/ Calcein mean intensity) upon treatment.
Functional Assessment of Drug-Induced Fluid Secretion Liabilities
Strengthen early GI risk evaluation with organoid swelling assay in patient-derived intestinal organoids. As a translational, phenotypic screening tool, this established workflow enables quantification of epithelial fluid transport upon drug treatment - a key driver of clinically observed drug-induced GI adverse events.
Imaging single organoids with dose-dependent quantification of swelling provides reproducible, data-rich functional insights into drug-induced gastrointestinal liabilities.
Figure: Swelling of patient-derived human intestinal organoids in response to Forskolin. Brightfield images show single organoids prior (T0) and 6h (T6) post Forskolin or DMSO (vehicle control).
Confidently Screen your Drug Candidates for Gastrointestinal Toxicity
By combining our drug-induced gastrointestinal toxicity (DIGIT) assay with the organoid swelling (DIGIT Plus) assay, we deliver reliable datasets for early lead optimization. Together, these complementary assays provide a comprehensive, human-relevant gastrointestinal safety profile to support early decision-making.
The DIGIT Plus assay comprises all DIGIT Assay endpoints and the organoid swelling assessment.
Combine predictive gastrointestinal toxicity testing with our 3D InSight™ DILI screening platform based on 3D human liver microtissues to obtain a broader safety profile early in drug discovery.
How to get started with our Gastrointestinal Toxicity Assessment
Starting your gastrointestinal toxicity assessment is simple and aligned with your discovery timelines. Submit your drugs, and our experts will manage the entire workflow: from standardized testing to automated data analysis.
For integrated drug safety profiling, gastrointestinal toxicity assessment can be combined with our industry-leading liver safety solutions, a gold standard in predictive DILI testing, enabling harmonized GI and hepatic risk evaluation through a single partner.
Select your assay
Choose between our standardized DIGIT assay or DIGIT Plus assay or combine both for comprehensive gastrointestinal safety profiling.
Submit your drugs
Ship your drug candidates
(2 weeks) before the treatment schedule. Our team coordinates logistics and prepares gastrointestinal organoid seeding in Gri3D® plates in parallel to align with the regular screening schedule.
Standardized screening & data analysis
We perform monthly high-throughput screening using patient-derived intestinal organoids and automated phenotypic imaging at single-organoid resolution.
Receive your decision-ready report
You receive a comprehensive report including quantitative results, IC₅₀ values, readouts to support confident go/no-go decisions.
Frequently Asked Questions
What is the 3D InSight™ Gastrointestinal Organoid model based on?
The 3D InSight™ Gastrointestinal Organoid model is based on patient-derived human small intestine tissue. The model originates from ethically sourced biopsies and is expanded as long-term organoid cultures. In addition to the small intestine model, our biobank includes organoids derived from colon, rectum, and stomach tissue. These additional GI segment models are currently available for custom projects.
What intestinal cell types are present in the 3D InSight™ Small Intestine Organoid model?
3D InSightTM Small Intestine Organoid model represents a physiologically relevant “mini-gut” and contains the key epithelial cell types found in native intestinal tissue. These include enterocytes, goblet cells, Paneth cells, and enteroendocrine cells. The presence of these cell populations is confirmed through gene expression analysis and immunostaining.
How are organoids cultured in Gri3D® plates? How long?
Organoids formation on Gri3D plates is driven by the sedimentation of uniformly distributed single cells into hydrogel microcavities without solid ECM. There cells aggregate and form organoids within each microwell with a dilute matrix cue that triggers polarization.
Small intestine organoids are typically cultured for 3-5 days to allow aggregation and organoid formation, followed by a 2-day drug treatment period for regular DIGIT or DIGIT Plus screening.
Is the 3D InSight™ Gastrointestinal Organoid model proliferative or differentiated?
The 3D InSight™ Small Intestine Organoid Model contains a mix population of both proliferative stem-cell and differentiated intestinal cell types. This balance enables physiologically relevant responses while maintaining proliferative capacity of the organoid.
Which organoid passage is normally used for DIGIT screening?
For monthly DIGIT screening studies, organoids are typically used within a defined, validated passage window, ensuring stability and reproductivity.
How often do you screen drugs using the small intestine organoid model?
Drug screening campaigns are organized on a monthly production schedule. Clients can submit drugs up to two weeks before the planned treatment start date. This structured workflow ensures standardized assay conditions and consistent data generation across studies. Check the DIGIT assessment schedule.
What is an organoid swelling assay in context of GI toxicity?
The organoid swelling assay is a functional assay that measures impact of drug response not linked to cell death. Upon drug treatment, organoids undergo phenotypic changes, for example swelling due to fluid movement into the lumen, reflecting possible disruption in epithelial ion channels activity.
What is Calcein AM/Ethidium homodimer-1 (EthD-1) live/dead staining?
Calcein AM/Ethidium homodimer-1 (EthD-1) live/dead staining is an image-based cytotoxicity assay performed directly on the Gri3D® plate to measure organoid viability after drug treatment. Calcein AM stains living cells green, while EthD-1 enters cells with damaged membranes and stains dead cells red. By quantifying the green and red signals, cytotoxic effects of test compounds can be measured at single-organoid level, enabling robust and precise IC50 calculation.
Can GI toxicity testing be combined with other readouts?
Yes. In addition to standard cytotoxicity endpoints, cell type specific toxicity assessment can be analysed and mechanistic readouts such as proliferative markers, junctional protein staining, inflammatory stimulation, or transepithelial electrical resistance (TEER) on organoid-derived monolayers can be incorporated in customized study designs.
