Bridging the gap
Drug-induced liver injury (DILI) remains the most common cause for acute liver failure in the world and is a leading cause of compound attrition in drug discovery. Although sufficient at capturing most intrinsic events, current models used in drug discovery have limitations as they are not effective at predicting or understanding more complex DILI events in humans. Furthermore, for testing new human-specific modalities, cell lines/animal models are less suitable due to genetic or immunological response differences. Using the PhysioMimix® Organ-on-a-Chip (OOC) System, human and preclinical animal microphysiological system (MPS) models have been developed to bridge these gaps.
Blogs
Organ-on-a-chip adoption: The roadmap to broader use
This blog explores challenges faced by the Pharmaceutical industry that pave the way for Organ-on-a-chip adoption and why it makes sense to start with toxicology workflows.
Posters
Developed the model, built the assay, now a focus on THROUGHPUT! The Liver-48, designed for industry adoption
The PhysioMimix® Liver-48 plate poster: CN Bio’s Multi-chip Liver-48 plate retains SBS-standard footprint, maintains Liver MPS functionality, and increasing throughput. By miniaturizing each chip, 48 tissues can be cultured per plate, 144 chips per PhysioMimix Single-organ HT System – more replicates and controls for fast, robust and cost-effective understanding of human drug safety earlier in the pipeline.
Blogs
Understanding the mechanism of toxicity: OOC’s crucial role
It’s commonly acknowledged that the current drug discovery process is inefficient with large numbers of drugs failing in the clinic. Almost a third fail due to undetected toxicity issues. Countless more potential drugs fail due to misclassification by animal models.
Webinars
Beyond hepatotoxicity red flags
Webinar Series 6 Episode 1
Standard preclinical approaches are poorly predictive, particularly for drugs eliciting human-specific toxicity or idiosynchratic DILI. In this webinar, Dr. Anthony Berger, a Field Application Scientist at CN Bio will discuss how liver-on-a-chip (LOAC) cocultures of primary hepatocytes offer a solution.
Webinars
Normalization of organ-on-a-chip samples
Webinar Series 6 Episode 2
Mass spectrometry based ‘omics pairs well with organ-on-a-chip-based investigations, which often have limited cellular material for sampling. A common issue with chip-based platforms is well-to-well or chip-to-chip variability in the proteome and metabolome due to many factors including plate edge effects, cellular asynchronization, effluent flow, and limited cell count.
Brochures & Flyers
Organ-on-a-chip Contract Research Services Brochure
Discover our full range of Organ-on-a-chip contract research services including ADME, NASH, DILI and Oncology as well as all the relevant endpoints.
Blogs
Immune-mediated DILI – Predicting the unpredictable!
Dr Anthony Berger discusses the limitations of the existing workflow and how organ-on-a-chip can help to predict the unpredictable, immune-mediated DILI.
Scientific publications
Normalization of organ-on-a-Chip samples for mass spectrometry based proteomics and metabolomics via Dansylation-based assay
Gallagher et al., 2022
This study shows the importance of normalization for paired MS-based multi-omics-OOC studies to accurately investigate highly toxic hazards and their effects on the human liver. Using VX, a highly toxic chemical compound, the study identifies VX-specific toxic effects on 3D liver tissues as well as specific hepatic cellular biomarkers and pathways affected by the toxic agent.
Application notes
Human liver microphysiological system for predicting the drug-induced liver toxicity of differing drug modalities
Novac et al
The liver is one of the organs most susceptible to drug toxicity and drug-induced liver injury (DILI). With more than 750 FDA-approved drugs known to have a degree of DILI risk, better preclinical models are required to de-risk new therapeutics earlier in the drug development process. We assess whether a Liver MPS model could be used to understand the detailed mechanistic aspects of liver toxicity.
Application notes
Microphysiological system for studying fatty liver disease and its impact on drug-induced liver injury
Kostrzewski et al
As a result of the increased prevalence of diabetes, obesity, and metabolic syndrome, non-alcoholic fatty liver disease (NAFLD) is now the most common chronic liver disease in developed countries. Using better in vitro models to fast-track therapeutic development but also accurately assess DILI risk in NASH patients ahead of the clinic is critical. Here, we show the potential of an in vitro 3D NASH model to accurately identify any DILI-associated risks.
Posters
Assessing drug-induced liver injury using a sensitive and selective human liver microphysiological system and clinical biomarkers
Novac et al
Drug-induced liver injury (DILI) is the most common cause of acute liver failure and a leading cause of compound attrition in drug development. In this poster, we demonstrate the potential of a liver MPS to better predict toxicity and improve in vitro to in vivo translation.