Zoë-CM2 is a ‘pivotal advancement’, according to the Boston firm, which develops and manufactures next-generation in vitro models that enable researchers to replicate and study human biology and disease.
The platform now incorporates enhancements that expand applications and reliability through remote operation, support, and ongoing software updates for researchers and drug developers, added the company.
Pioneered at the Wyss Institute for Biologically Inspired Engineering at Harvard University, Emulate’s Organ-on-a-Chip technology is designed to provide flexible microenvironments containing tiny hollow channels lined with living cells and tissues that can be subjected to mechanical forces that mirror breathing or digestion in the human body.
Targeted at industry, academic researchers, and government entities, the tools help experts understand and predict drug response with greater precision and detail than is possible with conventional cell culture or animal-based methods, said Emulate.
We spoke to Chris Hinojosa, VP of platform development for Emulate, to get a deep dive on the recent upgrade and how the company’s technology can generate novel scientific insights.
BioPharma-Reporter: What industry feedback informed the development of the Zoë-CM2 Culture Module?
Chris Hinojosa: “Our users wanted more real-time monitoring and feedback about the instrumentation’s performance, so that they can be confident that the results they obtain are due to the conditions they apply and not because of instrument performance. They also wanted to have more control over aspects of the microenvironment, and Zoë-CM2 enables us to develop and deploy those environmental control updates in a more efficient manner. We have also incorporated more automated routines that make the workflow easier for the end user.”
BPR: How is Zoë-CM2 a ‘pivotal advancement’?
CH: With the addition of internet connectivity, Zoë-CM2 gives users the ability to remotely monitor their study and update experimental settings, as well as easily audit historical pressure and stretch performance. It will also allow us to easily update capabilities over time, so users can develop an even greater range of organ models and applications than they can today. This will include regular, over-the-air software updates that will give researchers increased control over the cellular microenvironment, such advanced control overflow and stretch.
BPR: Is the Zoë-CM2 targeted at new or existing users?
CH: Zoë-CM2 is targeted at both new and existing users. New users will benefit from the new features Zoë-CM2 offers, and we have a trade-in program for our current users so they can upgrade and experience Zoë-CM2’s enhanced capabilities.
Zoë-CM2 is just one part of our complete Organ-on-a-Chip solution. The Orb Hub Module provides gas and vacuum stretch to Zoë-CM2, and Organ-Chip kits (available with or without Emulate-qualified human cells) are what customers use to build the advanced organ models that run on Zoë. Access to our suite of software applications—which enables study management, data analysis, and remote study monitoring and updates—is provided to our user community free of charge.
BPR: The Human Emulation System is said to enable more reproducible, physiologically relevant studies across a variety of organ models and applications – what organ models are currently available and typically what disease applications is it currently used for?
CH: Our validated organ models and applications include:
- Alveolus Lung-Chip: for customer-developed applications
- Brain-Chip: for modeling neuroinflammation
- Colon Intestine-Chip: for modeling inflammation, a mechanism in inflammatory bowel disease
- Kidney-Chip: for evaluating drug toxicity
- Liver-Chip: for evaluating drug toxicity
However, our system is designed to be flexible and organ-agnostic, enabling researchers across academia and drug development to design and build organ models of their own design to suit their needs. This includes research into viral and bacterial infection, colorectal cancer, leukemia, blood-brain barrier penetration, and more.
BPR: How does the system allow more accurate preclinical research programs?
CH: Regarding Zoë-CM2, specifically, because it automatically records instrument operations, users can view a performance audit trail and be assured their experiment ran as planned, giving them more confidence in their data.
Speaking to the Human Emulation System as a whole, there have been multiple publications demonstrating how researchers have been able to generate novel scientific insights compared to conventional in vitro or in vivo models. This includes research showing how:
- Liver-Chip has been used to accurately assess the toxicity of drugs whose toxicity was missed in preclinical testing with conventional animal and in vitro models.
- The Lung-Chip and Colon Intestine-Chip were used to assess the on-target/off-tumor safety risk of novel immunotherapies, where animal testing was uninformative due to the highly species-specific target expression and immune response involved.
- Colon Intestine-Chip was used to show that IL-22—a cytokine that is implicated in IBD but has had an unclear role based on mouse studies—has a damaging effect on the intestinal barrier, potentially clarifying its role as a barrier disrupter in IBD.
BPR: Can Emulate’s Organ-on-a-Chip solution enable preclinical research in central nervous system (CNS) diseases?
CH: Yes, researchers can use our Brain-Chip to model mechanisms of neurodegenerative disease and study the efficacy of therapeutics. We have validated an application for neuroinflammation, a mechanism implicated in neurodegenerative diseases such as Alzheimer’s disease. We also recently published research using αSyn fibrils to recreate and examine mechanisms mediating blood-brain barrier dysfunction—a key aspect in Parkinson's disease that remains poorly understood.
BPR: Does the system have microbiome applications?
CH: We are currently developing a validated microbiome application for the Colon Intestine-Chip. The Wyss Institute has also published research in Nature Biomedical Engineering with our Organ-Chips where they have demonstrated anaerobic microbiome culture in the Colon Intestine-Chip.
BPR: Can Emulate’s chips be used to determine the delivery mechanisms of something like an AAV gene therapy?
CH: Yes, with the Liver-Chip, we have been able to demonstrate dose- and time-dependent transduction of multiple AAV serotypes, something that is typically highly challenging with in vitro hepatocytes due to their limited gene expression. This is because the dynamic microenvironment and cell-cell interactions inside our Organ-Chips helps improve gene expression so it’s closer to in vivo.
BPR: To what extent can it mimic the human immune system?
CH: Two of our Organ-Chip models—the Liver-Chip and the Brain-Chip—include resident immune cells to capture cell-cell interactions more faithfully. In the Liver-Chip, this enables the assessment of immune-mediated hepatoxicity, while in the Brain-Chip, this enables researchers to model aspects of neuroinflammation, a mechanism implicated in many neurodegenerative diseases.
In collaboration with a pharmaceutical partner, we also published research incorporating circulating immune cells into the Lung-Chip and Intestine-Chip to assess the on-target/off-tumor safety of cancer immunotherapies. This type of therapy is increasingly difficult to study using animal models, as the antigens they target are often not expressed in animals. Conventional in vitro models meanwhile fail to replicate in vivo gene expression, limiting their value for these studies. Because Organ-Chips incorporate human cells, cell-cell interactions, and mechanical forces, gene expression is much closer to in vivo, enabling a more human-relevant and clinically translatable assessment of immunotherapy safety and efficacy.
BPR: What else makes the technology stand out when compared to conventional models?
CH: The same cell sources researchers use today—whether those are immortalized cell lines, primary human cells, or iPS-derived cells—can be used in our Organ-Chips. What our Organ-Chips offer is a better recreation of the cellular microenvironment, including mechanical forces as well as greater cellular complexity for improved cell-cell interactions. This results in improved gene expression that’s closer to in vivo that if the same cells were cultured in conventional platforms.
In the future we believe that Organ-Chips have the capacity to replace animal models; however, we need legislation such as the FDA Modernization Act and Humane Research Act that advocate for alternative methods to pass. In Europe, parliament has already called for a timeline to reduce and replace animal models for drug development.
BPR: In the long-term, is Emulate looking to expand the system to make it applicable to more drug modalities and organ/tissue types?
CH: Yes, we are continuing to develop new organ models and applications each year, with a focus of four key areas: immunology, cancer, microbiome, and ADME-Tox.
Additionally, we offer the Basic-Research Kit, which gives researchers the flexibility to create organ models of their own design.
BPR: How is the company planning to make the testing hardware as accessible as possible - an Organ-on-a-Chip on every benchtop – with expanded applications to become a standard in preclinical research?
CH: We are working closely with our user community and key opinion leaders to understand what additional organ models and applications are needed across biopharma and academia to improve human health. Over the coming years, our team of scientists and engineers will continue to expand our suite of validated, advanced in vitro models and applications so Organ-on-a-Chip technology can have a greater role throughout drug discovery and development. Meanwhile, we’re already working on how we can make our Organ-on-a-Chip culture platform more automated and hands-free, so more researchers can benefit from the technology, regardless of their experience level with advanced cell culture.