PhysioMimix^® Core Microphysiological System

Unlock a deeper understanding of human physiology and disease mechanisms to support target identification/validation. Microphysiological system (MPS) data complements data generated from patient-derived clinical samples, animal models and other in vitro preclinical tools by corroborating findings or identifying new avenues to explore.

Utilize disease models within late lead optimization to complement and inform in vivo efficacy studies, refine the effective therapeutic dose range and ensure only the most promising candidates progress to support a reduction in the number of animals required.

Use commonly affected human organ models to generate toxicology profiles and de-risk the development process. MPS provides a more sensitive way to uncover potential adverse effects and unlock the cause early enough to recover promising, but flawed, drugs, or progress those with clean profiles.

Exploratory cross-species in vitro toxicity tests using MPS minimise unnecessary animal use by flagging inter-species differences early and mitigating the risk of late-stage conflicting data or drug misclassification.

MPS models are highly metabolically competent, with expression of a full range of cytochrome p450s and transporters. Multi-organ models recreate the process of drug absorption and first-pass metabolism to derive bioavailability, offering enhanced accuracy versus animal models to improve the human translatability of preclinical ADME data

Cross-species MPS models are used as translational tools to troubleshoot contradicting toxicity data discovered during drug development. Their use provides clarity regarding which in vivo species is more human predictive when uncertainties arise.

In certain cases, OOCs provide a direct alternative to animals – especially where translatability to humans is poor. Human-specific drug modalities, for example, pose a significant development challenge as interspecies differences render animal models less suitable for safety, efficacy and ADME testing.

Where adverse toxicity effects are reported during clinical trials, MPS can be used for investigative purposes to recreate the clinical scenario and unlock the cause.

A wide variety of Organ-on-a-chip (OOC) / microphysiological systems (MPS) are now available for users and these OOCs vary in shape and format – from the more “simplistic” gravity-driven platforms, providing basic perfusion, through to complex microfluidics systems, that more accurately mimic the bloodstream, such as our PhysioMimix® Core microphysiological system. Each platform has its pros and cons and different contexts of use (COU), so different OOC technologies may be used together to improve the overall human relevance of your workflows. To help you establish which OOC technology is right for your needs, look at our “Top tips for integrating OOC technology into your workflows” infographic.

When comparing to chip-based technology with more physiologically relevant microfluidics, the main advantages of our PhysioMimix Core microphysiological system are described below:

Ease of use

Despite the complex biology that it mimics, the PhysioMimix Core microphysiological system is simple to install and integrate into existing workflows. Engineers are not required to install the platform; it can be set up in less than an hour by the user. The touch screen interface on PhysioMimix Controller units is user-friendly. Simply select the right program and press play, there is no need to fine-tune anything but the flow rate. We purposefully chose a plate-based design for consumables to decrease adoption barriers. Customers find the open architecture of our OOC system an advantage. For example, when inducing/studying the mechanism of disease or performing temporal studies, users can easily access cultures to change experimental conditions, manipulate the models, or remove samples.

To make it even easier to adopt, we also provide 3D validated cells and consumable plates with pre-coated scaffolds. For customers, who wish to recreate our Non-alcoholic Steatohepatitis (NASH) disease model, Drug bioavailability or Drug induced liver injury (DILI) assays in their own labs, we provide everything required in a kit format (NASH-in-a-box, Bioavailability assay kit: Human 18, DILI assay kit: Human 24).

Large-scale microtissues and media volumes

Up to 1.4 mL of media per sample, and microtissue can easily be recovered from our PhysioMimix Core microphysiological system, enabling deeper mechanistic insights to be derived when compared to alternative micro-scale chip-based systems. The open-well set-up of the Multi-chip plates allows for regular sampling of media, which can be analyzed to identify metabolized and secreted molecules over time, including clinical biomarkers, such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) for the liver.

The relatively large-scale recoverable microtissue allows for microscopy and -omics analysis (particularly next-generation sequencing, single cell sequencing, proteomics, lipidomics etc.), to be run in parallel on the same tissue.

Please visit individual application pages for a list of commonly derived endpoint measurements.

High assay sensitivity

The combination of physiologically relevant flow perfusion and the relatively large, human-relevant microtissues generated by the PhysioMimix Core microphysiological system, provides high assay sensitivity, as explored in more detail in this blog: De-risking drug-induced liver injury through the predictive power of organ-on-a-chip

Single and multi-organ capabilities

The PhysioMimix Core provides both single-organ and multi-organ capabilities, the latter of which enables bioavailability determination, complex investigational toxicology studies, and the discovery of insights that can only be derived by interconnecting organs and tissues together into systems.

Throughput and cost/sample

Our systems offer one of the highest throughput capabilities in class. The multi-chip plate-based approach has the added benefit of being easily scalable compared to most other OOC solutions. Each PhysioMimix Core controller can run up to six Multi-chip plates at a time. Each of our plates incorporates 6 to 48 chips, offering you the advantage of running from 6 to 288 samples simultaneously. This approach also benefits from a reduced cost per sample.

Low non-specific binding consumables

Most chip-based technologies use polymethylsiloxane (PDMS) to create their chip and microfluidics. However, drugs are known to bind highly and non-specifically to PDMS, which introduces inaccuracies when assessing a compound’s dose-dependent effects. When developing our PhysioMimix Multi-chip plates, we chose to use cyclic olefin copolymer (COC) because of its low non-specific binding properties to avoid these concerns (Tsamandouras et al., 2017).

Recapitulating the immune system

Another advantage of our PhysioMimix Core microphysiological system is that users can add in both innate, i.e. tissue-specific immune cells, and circulating immune cells to their experiments to assess immune responses. Unlike most chip-based OOC technologies, which are designed with flushing-type microfluidics, in which the liquid is flushed from one side of the chip to the other, the PhysioMimix Core allows media to recirculate through or around the cellular tissue, making it easier to investigate immune-mediated responses.

Close collaborative links to the US FDA and other regulators

We have a long-standing collaboration with multiple research groups within the U.S. Food and Drug Administration (FDA). This led to a co-publication, where the PhysioMimix Liver-on-a-chip (or Liver MPS) model was compared to the gold standard of in vitro liver cell culture (Rubiano et al, 2021). This first-ever co-publication between a regulator and an OOC developer showcases the great potential of OOC technologies for improving the predictivity of preclinical drug development. Additionally, we are participating in a 3Rs Collaborative-led project with the FDA to build confidence in Liver MPS for DILI. For further information about additional consortia, groups and networks that CN Bio is actively involved with, please see our About us page.

Watch a short 15-minute presentation that provides a direct comparison of traditional approaches to genotoxicity testing and commercially available OOC technologies from collaborators at Charles River Laboratories.

By combining the strengths of all our existing suite of instruments PhysioMimix Single-organ, Multi-organ and Higher throughput (HT) Systems into one intuitive and universal platform, we’ve created a solution that delivers ultimate flexibility alongside physiological precision and ease-of-use.

Launched on October 14th 2025, PhysioMimix Core is the first Organ-on-a-chip (OOC) solution that delivers validated performance across all configurations within one easy to adopt, adapt and scale microphysiological system (MPS).

Our goal for the PhysioMimix Core System is to empower you with a future-proofed solution that unlocks deeper insights into human biology.  With PhysioMimix Core, you gain unprecedented control and scalability to push boundaries and accelerate breakthroughs across the drug development pipeline.

Our PhysioMimix Core Microphysiological system currently offers medium throughput. Each Controller can run up to six Multi-chip plates simultaneously, with 6, 12, or 48 wells incorporated within each Multi-chip plate. The number of chips available per plate is determined by the plate type – the Dual-organ plate contains six wells/chips per plate, our Barrier plate contains 12, and our Liver-12 and Liver-48 plates, as the name suggests, contain either 12, or 48 chips per plate.

There is generally an inverse relationship between throughput, physiological relevance and data depth. High-throughput in vitro screens are often performed using simplistic, convenient 2D immortalized cell-based assays. They provide a low number of output measurements from which yes/no decisions are made at scale. However, their ability to predict human outcomes is relatively low. OOC assays offer the opposite, as described and explored in more detail.

In short, OOC assays offer advantages for early-stage target identification/validation, lead optimization and late-stage preclinical drug evaluation phases of the discovery and development pipeline. Here, fewer compounds are screened in complex human-relevant preclinical assays that use primary cells. These assays deliver greater sensitivity, higher-content data to provide deeper mechanistic insights and improved data translatability into the clinic.

ysioMimix Core Microphysiological system currently offers medium throughput. Each Controller can run up to six Multi-chip plates simultaneously, with 6, 12, or 48 wells incorporated within each Multi-chip plate. The number of chips available per plate is determined by the plate type – the Dual-organ plate contains six wells/chips per plate, our Barrier plate contains 12, and our Liver-12 and Liver-48 plates, as the name suggests, contain either 12, or 48 chips per plate.

There is generally an inverse relationship between throughput, physiological relevance and data depth. High-throughput in vitro screens are often performed using simplistic, convenient 2D immortalized cell-based assays. They provide a low number of output measurements from which yes/no decisions are made at scale. However, their ability to predict human outcomes is relatively low. OOC assays offer the opposite, as described and explored in more detail in this blog.

In short, OOC assays offer advantages for early-stage target identification/validation, lead optimization and late-stage preclinical drug evaluation phases of the discovery and development pipeline. Here, fewer compounds are screened in complex human-relevant preclinical assays that use primary cells. These assays deliver greater sensitivity, higher-content data to provide deeper mechanistic insights and improved data translatability into the clinic.

Absolutely, expanding the number of microtissues from 12 to 48 per plate, by using Multi-chip Liver-48 plate, enables you to run multiple dose-responses within a single plate. You can run two dose-response curves (seven concentration points per curve) on a single plate, or more dose-response curves with fewer points, plus controls, in triplicate. An advantage we are excited about is the added data consistency this approach offers; because all your samples are housed within a single plate, you minimize the inherent variability that comes from using multiple plates or chips for the same experiment.

There is an added cost advantage to using the Liver-48 plates. As the system is miniaturized from our Liver-12 plates, everything (cells, media, reagents) is about 75% smaller, which means your running costs per condition reduce proportionally.

otissues from 12 to 48 per plate, by using Multi-chip Liver-48 plate, enables you to run multiple dose-responses within a single plate. You can run two dose-response curves (seven concentration points per curve) on a single plate, or more dose-response curves with fewer points, plus controls, in triplicate. An advantage we are excited about is the added data consistency this approach offers; because all your samples are housed within a single plate, you minimize the inherent variability that comes from using multiple plates or chips for the same experiment.

There is an added cost advantage to using the Liver-48 plates. As the system is miniaturized from our Liver-12 plates, everything (cells, media, reagents) is about 75% smaller, which means your running costs per condition reduce proportionally.

otissues from 12 to 48 per plate, by using Multi-chip Liver-48 plate, enables you to run multiple dose-responses within a single plate. You can run two dose-response curves (seven concentration points per curve) on a single plate, or more dose-response curves with fewer points, plus controls, in triplicate. An advantage we are excited about is the added data consistency this approach offers; because all your samples are housed within a single plate, you minimize the inherent variability that comes from using multiple plates or chips for the same experiment.

There is an added cost advantage to using the Liver-48 plates. As the system is miniaturized from our Liver-12 plates, everything (cells, media, reagents) is about 75% smaller, which means your running costs per condition reduce proportionally.

Our PhysioMimix^® Core microphysiological system is comprised of a controller unit (which controls and regulates the microfluidics), an umbilical cable (comprising three pneumatic tubes), an electrical cable, a docking station, and drivers.

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1. Controller
2. Docking station(s)
3. Driver(s)

The PhysioMimix Core controller can operate up to six Multi-chip plates in parallel, using two docking stations. Each Multi-chip plate is inserted into a bespoke MPS Driver. Up to three Drivers can be connected to each Docking station.

System setup is very straightforward! It should take you less than one hour. Instructions are provided within the instruction manual, or in video format, to guide you through the process. No specialist engineers are required.

First, you have to install the controller on your lab bench or sturdy table next to the incubator. Next, connect the colour-coordinated cables, following the instructions in the manual. Then, pass the umbilical cable into the rear (or side) port of the incubator. Place the docking station onto the middle shelf of the incubator, and connect the cables following the same color patterns. Switch on the power on your controller and you are ready to use your system. Experimental setup is achieved using the intuitive touchscreen on your controller unit.

However, if you require any additional support installing your new system, our Field Application Scientists are also available to guide you through the process.

Our system is compatible with any standard laboratory incubator with a side or rear access port. The docking station fits comfortably on the shelf of a standard incubator and is connected to the main controller unit via the umbilical cable that is inserted through the access port.

Our PhysioMimix Core microphysiological system has been designed with minimal maintenance requirements in mind. Each chip, within our consumable plates, contains integrated fluid handling pumping to mimic blood flow. This all-in-one tubing-free solution eliminates the requirement for expensive pumps and flow regulators, minimizing the need for routine sterilization. The biological materials – tissue and media- remain contained within the pre-sterilized, single-use consumable plates, which are disposed of (in accordance to Health and Safety protocols) at the end of your experiment.

After the experiment, a simple wipe down with 70% ethanol is sufficient for most systems. If the system is used for culturing unscreened cells or cells transfected with a virus, it should be decontaminated with detergent or bleach and then wiped down with 70% ethanol.

It is straightforward to transition from 2D cell culture into 3D culture using our PhysioMimix Core microphysiological systems.

Firstly, the PhysioMimix Core system is very easy to set up and user-friendly. The hardware takes less than an hour to install and does not require an engineer to be on site. Our PhysioMimix Multi-chip consumable plates feature an open-well design that will feel familiar to anyone who works with standard cell culture plates. They are ready to use as supplied, i.e., Liver plates are pre-coated with extracellular matrix to promote cell attachment. This approach lowers the adoption curve versus other smaller futuristic-style chips. Some elements of assay set-up may be new to users, such as priming the plates’ microfluidic pumps prior to cell seeding, but these are not complex procedures.

Additonally, we offer online and onsite training, plus a range of SOPs and “how-to” videos. To learn more about our Training and support programs, visit our support page or contact us.

Cell quality is critical to the success of OOC assays, so pre-validating your cells is very important. Save valuable time, resources, and budget quality controlling cell lots for OOC compatibility by leveraging our catalog of 3D validated cells. Our primary cell lots have been thoroughly tested to ensure that they thrive in 3D tissue culture, maintaining their function and phenotype for up to 4 weeks under perfusion using the PhysioMimix System. This blog: A guide to pre-validating primary cells for use in Organ-on-a-chip assays provides a useful overview of some of the considerations to keep in mind when validating cells for use in OOC assays.

We are also offer all-in-one kits – NASH-in-a-box, DILI assay kit: Human 24, Bioavailability assay kit: Human 18, which contain everything you need to recreate our in vitro MASH model, DLI and bioavailability assays, respectively, in your own laboratory.

At CN Bio, the success of our users is critical to our own success. Therefore, we ensure that customers can successfully generate 3D in vitro microtissues right from the start of their journey with us. Despite the complexity of the biology that PhysioMimix OOC systems create, our new users always find the process surprisingly simple! In this blog: Debunking the 9 myths of Organ-on-a-chip technology, we explore and address some of the myths associated with OOC.

Our PhysioMimix Core microphysiological systems and Multi-chip plates have been designed to be highly adaptable to a wide range of cell types, including primary cells, cell lines, induced-pluripotent stem cells (iPSC) and tissue biopsies.

The PhysioMimix Core microphysiological systems is an open and versatile system that can be used to culture human and animal MPS models. In 2025, we launched our enhanced DILI Contract Research Services featuring the rat (Sprague-Dawley) and dog (Beagle) primary Liver MPS models, for comparative analysis and cross-species insights.

Our collaborators at Texas A&M University used the PhysioMimix Core microphysiological system to develop Liver MPS models from human, monkey, rat, and dog hepatocytes. These models were then evaluated alongside equivalent 2D cultures, compared with each other, and benchmarked against in vivo data to assess their ability to detect drug toxicity. The team found that liver function was more stable in the PhysioMimix Liver MPS compared to 2D cultures. They also observed that the MPS more accurately captured species-specific toxicity patterns. Additionally, the PhysioMimix LC12 model demonstrated reproducible results across experiments. Read the scientific publication to learn more about their findings.

Our work at CN Bio has mainly focused on combining physiologically relevant ratios of primary human cells to recreate human microtissues for drug discovery. However, when we first developed our prototype technology (the Legacy^© system) with Professor Linda Griffith’s team at MIT, we used primary rat and human hepatocytes. For some applications, such as developmental and reproductive toxicity testing, it makes sense to use animal cells as animal models are the gold standard for decision-making.

Additionlly, our collaborators at the Pirbright Institute, are working with alternative species; currently using the PhysioMimix Core microphysiological systems to develop avian models to study avian flu and other viruses.

It is important to note, the key to successfully culturing non-human MPS models, lies in selecting the right extracellular matrix (ECM) to support the tissue and cell adhesion, and optimization of cell culture conditions.

Our PhysioMimix Core microphysiological system can be used for both single-organ and multi-organ studies. Multi-organ studies are performed using the PhysioMimix Multi-chip Dual-organ plates that house six barrier (gut, lung etc.) chips fluidically-linked to six Liver chips. Cell culture media is pumped between these chambers in a manner that mimics blood flow in the body.

Dual-organ plates

Using this approach, we can model organ-organ interactions to discover how secreted markers from one organ affect a second to explore multi-organ toxicity, immune-mediated toxicity or drug bioavailability, for example.

Considerable advances have been made in culturing cells to form human-like tissues at a microscale. The properties of cellular microenvironments in vivo vary from tissue to tissue, and therefore different approaches are used for recreating the microenvironment for different tissue types in vitro.

Depending on tissue type, the aim is to:

• enable 3D culture or co-culture of different cell types
• expose cells to microfluidics and electromechanical cues
• culture cells with polarity as tight barrier-like monolayers
• deliver chemical signals
• use engineered and functionalized extracellular matrices, among other techniques in the field of bio-microfabrication

The PhysioMimix Core microphysiological system offers precise control of media flow rate that mimics blood flow. Inter-organ and intra-organ flow rates can be adjusted using the touchscreen interface of the PhysioMimix Core Controller unit.

The Controller unit provides precise and controllable flow via a pneumatic connection to each chip within the Multi-chip plates. A docked plate aligns with the pneumatic lines in the system and connects with the PhysioMimix Core Controller. Each chip contains integrated fluid handling pumping to mimic the bloodstream. The in-plate pumps and valves are then actuated by under-plate pneumatics to create flow, as demonstrated in the diagrams below.

Liver-12 plates

Barrier plates

Dual-organ plates

If you require further guidance on the optimal flow rate for your organ model, we provide flow rate recommendations for the organ models we have developed and validated.

This approach means that PhysioMimix Core microphysiological systems contain fewer moving parts for system reliability.

For a detailed explanation, please watch the on-demand webinar: The Rhythm of Life.

Recirculating fluidic flow mimics the bloodstream, delivering biomechanical stimulus, oxygen, nutrients, and removing waste from 3D cell cultures. Flow perfusion enhances microtissue viability, function and phenotype, and maintains cultures for up to one month.

Further details can be found in our blog: Flowing to the beat of your heart and on demand webinar: The Rhythm of Life.

Extensive research has been conducted to ensure the flow rates delivered by our PhysioMimix Core microphysiological system match the organ-specific flow rates required by their in vivo counterparts.

Domanskyt et. al. detail how we calculated the flow rate for the liver model when developing the PhysioMimix system in collaboration with MIT. Further details can be found in the publication: Perfused multiwell plate for 3D liver tissue engineering (Domansky et al, 2010).

Note that fluidic flow rates were calculated for single (Gut and Liver) organ models. When considering multi-organ models, the calculations to determine fluidic flow rate and cardiac output for each organ, and between organs is more challenging. The more organs that are incorporated into the model, the more parameters must be considered. A good example of this can be found in our four-, seven- and 10-organ model publication: Interconnected Microphysiological Systems for Quantitative Biology and Pharmacology Studies (Edington et al, 2018).

When recreating models developed by our scientists, we recommend using the flow rates provided. These have been fine-tuned to accurately recapitulate tissue exposures within the human body. However, you can change both the flow rate and the direction of the flow as needed to fit your experimental design and context of use, using the PhysioMimix Core Controller.

Our pumps are optimized to work in the low µL.s^-1 range as this net flow rate sits well within the requirements of our overall system design – total volumes, re-oxygenation rates, and mass of tissue being perfused. Our design allows for significantly lower or higher net flow rates, but there is currently no biological need for this.

The PhysioMimix Core microphysiological system provides you with complete control at each step of your experiment, starting from cell seeding and microtissue formation, to dosing. This is particularly enabling should you wish to develop a new model using the platform. When developing multi-organ models, leveraging our Dual-organ plate, you can optimize both the inter-organ flow rate, for accurate on-platform pharmacokinetics, and the intra-organ flow rate, to optimize oxygen and nutrients intake as well as mechanical forces.

Besides perfusion flow rates, it is important to consider the physical and chemical properties of the tissue scaffolds (biocompatibility, geometry, surface hardness, wettability), as well as the chemical and biochemical makeup of the media. These help mimic the environment the tissue encounters in vivo and are therefore important for the experiment.

However, to develop a commercially accessible product, there are several further aspects to consider. These include multidisciplinary considerations:

• Usability (ease-or-use, access to the tissue and media for sampling, preventing infection and contamination)
• Throughput (how many replicates can be simultaneously run)
• Ease of manufacture (reproducibility, quality control, sterilization methods, packaging, and shelf-life)
• Regulatory aspects, as every product needs to be proven safe and effective

Our PhysioMimix Core microphysiological system is generally agnostic to drug type, providing compatibility with small or large molecules and newer drug modalities. In a recent Application Note, we assessed the Drug-liver injury (DILI) potential of two antisense oligonucleotides (ASOs) using our Liver MPS model. Collaborators have also used our liver model to investigate the uptake and distribution of ASOs within liver tissue.

The advantage of OOC technology is that it provides a humanized test system that can be used to assess drugs with human-specific modes of action. There is much interest in the potential of Organ-on-a-chip technology in this area, due to the spiraling costs, limited accessibility, and ethical concerns surrounding the use of non-human primates (NHPs). A more comprehensive overview of this topic is provided in this recent article: Organ-on-a-chip models in drug development in Drug Discovery World.

Organ-on-a-chip (OOC) or microphysiological systems (MPS) can be used for testing genetic engineering therapeutic agents, including adenovirus-associated viruses (AAV) and adenovirus, ASOs, small interfering RNAs (siRNAs), and CRISPR agents. The longevity of MPS cultures makes them particularly well-suited to studying these agents, which need time to establish in cellular systems before having an efficacy or toxicological effect. Additionally, most of these agents are human cell or target-specific, making primary human OOC models ideal for their testing.

We completed the DARPA body-on-a-chip program with MIT, which set the ball in motion towards the development of complex and interconnected systems using four-, seven- and 10-interconnected MPS (Edington et al, 2018). The exciting undertaking uncovered many challenges with regard to scaling and interconnection that are still being optimized for commercial settings. For example, developing a common medium for all interconnected organs is a necessary step, but developing a universal solution that maintains the health, phenotype, and function of many organs is not a simple task in practice.

Additionally, the more organs that are interconnected, the more complex the system microfluidics becomes. Ideally, system microfluidics should recreate a physiologically relevant flow rate and cardiac output within each organ, as well as between the organs in the system. Plus, the solution needs to offer ease-of-use, with the ability to mix-and-match different organ combinations – a prerequisite for easy integration into laboratory workflows. To provide user-friendly workable solutions for use in commercial settings, we have stepped back from the full body-on-a-chip of DARPA days and have taken our time to develop gold-standard single-organ and dual-organ models to form less extensive but more usable multi-organ systems that provide the next dimension of drug safety and bioavailability in vitro data.

By connecting liver tissue with another “route of entry” organ (gut/liver or lung/liver models), PhysioMimix users can now study reactive metabolite-driven toxicity whilst simultaneously evaluating drug absorption, metabolism, and bioavailability.

The more we develop and understand complex models, the easier it will be to develop body-on-a-chip models for applications such as personalized medicine, but this is not something we see happening in the near future. Although CN Bio’s vision is to become the first commercialized body-on-a-chip provider, we currently see a greater value in developing a broader portfolio of applications for single- and dual-organ models, which will enable end-users, particularly in the pharmaceutical industry but also wider industries such as cosmetic or food, to benefit from improved data translation over standard techniques.

The complexity greatly depends on the cell types used, the organ models and application in question.

For our Gut/Liver model and ADME assays, slight optimization is required. At the start of the experiment, each organ is cultured individually until the tissues are fully formed. Gut cells are seeded and grown on the apical side of a Transwell® insert, and liver cells are seeded directly into the liver chamber of the Dual-organ plate. Once the organs are cultured, flow between the compartments is activated and drugs are added. However, the gut’s media remains separated by the Transwell insert, its membrane, and the physical barrier of the gut microtissue. Only the drugs that are absorbed by the gut, transfer to the basolateral side of the chamber and into the media that supports liver function.

However, for both organ tissues to be seeded directly into the Dual-organ plate, one common media is required to maintain tissue health, phenotype, and function. This requires optimization, with further consideration for the application. For example, serum is usually used to culture Caco-2/goblet cells, however, for PBPK studies we use a serum-free gut media to reduce the risk of the drug binding to serum proteins. Gut cells tolerate this remarkably well with no drop in epithelial barrier integrity (TEER).

All three basal media (for liver, gut, and gut/liver cultures) are provided as part of our fully human PhysioMimix Bioavailability assay kit: Human 18. For faster Gut/Liver MPS model and bioavailability assay adoption, the all-in-one kit provides everything you need.

Thanks to the large sampling volumes of the system (up to 1 mL of media and relatively large 3D tissues grown on scaffolds, or Transwell® inserts), a wide and diverse set of end-point parameters can be measured from each sample – either by repeat sampling over time and/or at the termination point of the experiment. These include microscopy, histology, biomarker expression, metabolite profiling, toxicity profiling and -omics analysis.

Please visit individual application pages for a list of commonly derived endpoint measurements.

Absolutely yes! The PhysioMimix Core microphysiolical system’s Dual-organ plate allows for a large volume of media (up to 1.4 mL) and tissue to be sampled, enabling pharmacological and toxicological studies to be combined. For example, using the Gut/Liver model to mimic in vivo drug transit conditions, on-board pharmacokinetic profiles for the drug can be generated. The exposure of the target tissue to a dynamic concentration of the drug’s metabolites can then be assessed, from which any toxic effects can also be determined.

Organ-on-a-chip (OOC), or Microphysiological systems (MPS), are fast-developing technologies that can be used for various applications within the drug discovery and development process. The evaluation of these technologies versus specific contexts of use is ongoing and involves comparison to preclinical and clinical data sets to understand translation between these complex in vitro models and humans. Overall, a cellular microenvironment with physiological properties can prolong, enhance, enable, or stabilize the function of tissue-specific cells relative to traditional culture systems. The next step is evaluating how well OOC/MPS models predict clinical results. For this purpose, OOC systems should be tested for specific contexts of use (COU) using assays and compounds (with controls) that are related to each context of use.

In benchmarking studies, we compare our organ-on-a-chip data against clinical data for reference compounds. Tsamandouras et al, 2017 is a great example. In this collaborative study with Prof. Linda Griffith’s lab at Massachusetts Institute of Technology (M.I.T.), various well-known drugs (e.g.: lidocaine, ibuprofen), were investigated to establish translatability between the OOC model and human hepatic drug metabolism. This study also successfully predicted the associated in vivo population variability by exploring donor-donor variability in in vitro OOC models too. A second example is Sarkar et al 2017, who published their integrated assessment of Diclofenac biotransformation, pharmacokinetics, and omics-Based toxicity in a three-dimensional human liver-immunocompetent co-culture system. These and other publications are cited in this article written for Drug Discovery World.

This area is also being explored in more detail by our collaborators at the US FDA too. Collaborations with the FDA began in 2017, to evaluate our PhysioMimix OOC microphysiological systems for investigating critical drug parameters, including metabolism, toxicity and drug-drug interactions. Concluding in 2021, the FDA published a paper outlining the accuracy and reproducibility of the liver-on-a-chip model, alongside its enhanced performance over conventional techniques.

Building on success, our partnership has since expanded twice– in May 2021 and January 2023, further demonstrating the value of human predictive single-and multi-organ models within the drug discovery and development space.

In 2021, the expansion sought to further investigations into CN Bio’s liver-on-a-chip, as well as opening a new project to assess our lung-on-a-chip model for studies involving inhaled drug products.

Most recently in 2023, research turned to CN Bio’s multi-organ MPS, aiming to investigate the accuracy of the PhysioMimix Multi-organ System for human drug bioavailability studies, with a goal to better inform dosing regimens to improve efficacy and limit side effects.

Additionally in 2025, we are participating in a 3Rs Collaborative-led project with the FDA to build confidence in Liver MPS for DILI.

In 2025, our collaborators at Texas A&M University found that MPS model detected species-specific differences in drug response, with human hepatocytes showing robust and clinically relevant toxicity profiles for DILI compounds, showing both physiological and clinical relevance. (Negi et. al., 2025)

Please also read our Application Notes for more examples of benchmarking studies versus specific contexts of use.

We use a variety of scaling methodologies and do not have a one-size fits all approach. Most commonly, we focus on a functional methodology to scale microtissues to ensure crosstalk between organs is physiologically relevant, but other methods are available. For example, to scale and extrapolate in vitro data generated from our PhysioMimix Core microphysiological system into an in vivo prediction, we use physiologically-based pharmacokinetics (PBPK) modeling. By comparing the behavior and toxicity of a compound in our Gut/Liver MPS to PBPK, we provide users with a physiologically relevant picture of a drug’s behavior and the crosstalk between primary human gut and liver tissues. To know more, read our latest publication Abbas et al., (2025).

Collaborators at Roche have also used this methodology in their recent publications (Milani et al 2022 and Docci et al., 2022) using a Caco-2 Gut/Liver model, and a liver-only model, respectively.

This has been explored by Franzen et al., in 2019. Their independent research estimates that fully integrating OOC into pharma workflows could save up to 10-26% of all R&D costs: US$49bn a year, driven by changes in direct costs, success rates and the length of the R&D process. They predict that the most impacted phases are the lead optimization and preclinical phases of R&D.

At CN Bio, we are working on our own package of information to highlight the potential economic benefits of OOC.

The first output from this project is a 2-page document which summarizes the highlights of a KOL panel discussion and market research survey results (125 respondents completed in early 2023 by the Pharma Intelligence group, Citeline), which can be downloaded. Also, you can access the full survey results.

It is important to highlight that OOC/MPS models were not originally designed to replace animal models but to provide researchers with an investigational tool to use alongside current in silico, in vitro and in vivo models to address the translatability limitations of preclinical assays, including animals.

Our aim for OOC is to reduce the number of test compounds that require in vivo animal studies by deriving better insights ahead of time, such that only the very best drugs make it through and their ADME/Tox profiles are well-defined. As a result, the number of animals required to test them will lessen. Should there be a time when superior performance is proven, we hope that OOC models will eventually replace animal use. This point is explored in more detail in this Medicine marker article.

Also, as new human-specific drug modalities continue to emerge, the need for more predictive preclinical models is more important than ever. Coupled with increasing awareness around ethical considerations and the spiraling cost of animal experimentation, there is growing interest in the development of New Approach Methodologies (NAMs), such as OOC, that enable researchers to design more predictive and cost-efficient in vivo studies that reduce the number of animals required. Recent ground-breaking legislation, including the US Government’s FDA Modernization Act has opened the door to more widespread NAM adoption.

The U.S Food and Drug Administration (FDA) has also recognized the potential for MPS to improve the predictability of drug discovery. Through collaboration, the FDA is evaluating the performance of PhysioMimix OOC models versus gold standard techniques. In a recent publication (Rubiano et al., 2021), the superior performance of the PhysioMimix’s Liver-on-a-Chip model (for applications that include drug metabolism, safety, and accumulation) over traditional approaches was demonstrated. The data within this study provides decision-makers with the collateral to justify the adoption of MPS into their workflows and, by adopting these powerful systems, we offer an option to help reduce and refine the number of animal tests with a view to their future replacement. The FDA has since expanded their collaboration with us (in 2021 and, 2023), to explore additional single- and multi-organ models and their specific contexts of use, including our Lung-on-a-chip model for studies involving inhaled drug products and multi-organ models for human drug bioavailability studies.

The study of fatty liver disease represents another area where improved models are desperately needed, as animal models do not adequately represent the pathophysiology of complex human metabolic diseases such as Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as Non-alcoholic fatty liver disease (NAFLD), and Metabolic dysfunction-associated steatohepatitis (MASH) previously known as Non-Alcoholic Steatohepatitis (NASH). This topic is explored in detail in this blog: Of Mice and Men – Will human organ-on-a-chip disease models replace animal use? and article: A pressing need for accurate preclinical models of metabolic disease.

By comparison, our PhysioMimix MASH model demonstrates an improved alignment of transcriptomic profiles compared to human data and more closely replicates changes found in MASH patients than the murine WD model (Vacca et al., 2020), improved pathophysiology that more accurately recapitulates long-term fibrotic and inflammatory MASH phenotypes (Kostrzewski et al, 2019) versus traditional approaches and delivers more clinically relevant responses in response to therapeutic challenge. If you’d like to know more about this model please visit our application page, watch our on-demand webinar: Pathologically scarred by fibrosis: How to model and quantify human NASH in a microphysiological system in collaboration with AstraZeneca.

Our collaborators at Charles River Laboratories have developed a cost-effective Liver MPS model using PhysioMimix Core microphysiolocal system that provides a reliable assessment of a compound’s genotoxicity in the human liver compared to gold-standard animal models. If you’d like to know more about their work, you can watch their on-demand presentation from SOT 2023.

Additionally, for safety assessment applications, it would make sense to recreate species-specific rat, dog, and non-human primate OOC models, since animal models are the gold standard for decision-making. We are currently qualifying the use of non-human cell types to show the translatability of data generated by PhysioMimix OOC to in vivo animal models.

We also work collaboratively with organizations such as The North American 3Rs Collaborative (NA3RsC) and Animal Free Research UK (AFRUK) to drive awareness for OOC/MPS technology as an animal alternative.

The topic of where and for what purposes microphysiological systems (MPS) otherwise known as Organ-on-a-chip (OOC) can be used is explored in detail in these articles written for International Biopharmaceutical Industry and Drug Discovery World.

In summary,

• Microphysiological systems can be used right at the beginning of drug discovery to identify and validate targets in models that more accurately represent human disease.
• Through the generation of human translatable safety, efficacy and ADME data, OOC present an opportunity at the lead optimization stage to re-engineer potentially flawed drugs early to maximize their chance of success once they reach the clinic.
• In the drug development phases, MPS can be used ahead of animal studies to test larger numbers of conditions, refine conditions, or minimize the number of animals required for safety, efficacy and ADME studies.
• MPS can be used alongside animals to confirm or query results, reducing the risk of unforeseen issues due to interspecies differences.
• In certain scenarios, MPS provides an animal alternative, minimizing the unnecessary use of animals where translatability to humans is poor, i.e., where preclinical animal models do not exist (e.g., Hepatitis B virus (HBV) infection), or for the testing of drugs with human specific modalities which require testing using non-human primates, the latter of which are extremely costly, ethically undesirable and challenging to source.

Additionally, recent market-led information regarding this topic can be found in this document summarizing the highlights of a KOL panel discussion and market research survey results (125 respondents completed in early 2023). You can access the full survey results here.

Yes, ground-breaking legislation, including the US Government’s FDA Modernization Act has opened the door to more widespread New Approach Methodologies, also known as New Alternative Methods, or NAMs, which include Organ-on-a-chip (OOC).

The impact of the FDA Modernization Act 2.0 is explored in detail in this blog: The U.S. FDA Modernization Act 2.0. Now the animal testing mandate is removed, learn what can be embraced in its place. However, the key take-home messages are that the federal mandate stipulating that drug testing in animals must be performed, has now been eliminated. The use of NAMs to establish drug safety and effectiveness may be adopted in place of animal testing, where appropriate.

In Section 3209 of the FDA Modernization Act 2.0 entitled “Animal Testing Alternatives,” the bill amends the regulatory guidance at the FDA that requires animal testing for drugs and biosimilars. The bill amends the Federal Food, Drug, and Cosmetics Act (FFDCA) to:

• Substitute the term “nonclinical tests” for the current “preclinical tests” (including tests on animals),
• Substitute the term “animal” for “nonclinical tests” and,
• Add a new section defining “nonclinical tests” to include human-relevant testing methods such as cell-based assays, microphysiological systems (such as Organ-Chips), or bioprinted or computer models.

It’s important to note here that, although the U.S. has been the first regulator to take the leap, and North America in general are leading the way, important work is going on in other regions to drive change too as regulators acknowledge that animal testing for the sake of animal testing is not the way forward. Back in 2014, in the U.K., plans were announced to reduce the use of animal tests in scientific research, aiming to replace those tests with ‘scientifically valid alternatives’ where possible. More recently in 2021, the European Parliament voted in favor of plans to phase out animal testing in research.

In 2022, CEN, the European Committee for Standardization – who are focused on helping to drive the adoption of new technologies – set up a focus group on OOC and not-for-profit groups such as The European Organ-on-a-Chip Society (EUROoCS) have been growing their network since 2018 in a bid to share and advance knowledge in the field towards better health for all.

However, OOC is still a developing field and some challenges need to be addressed before its data is widely accepted by regulatory agencies. These include demonstrating the reliability and predictive power of OOC versus specific contexts of use, standardization regarding how OOC models are developed and validated, plus guidance regarding how to use OOC data in regulatory contexts. For this reason, we are currently participating in a 3Rs Collaborative-led project with the FDA to build confidence in Liver MPS for DILI.

Behind the scenes, companies like ours have been developing technology, the advanced single- and multi-organ models and their applicability (within the disease modeling, toxicity testing and ADME space) for over a decade. Through collaboration with academia, drug discovery companies, consortia (such as the IQ Consortium) and various regulators (including the FDA), we have collectively been growing a body of evidence to demonstrate the ability of these human-relevant models to deliver data that better predict human outcomes, and to overcome the aforementioned challenges.

In December 2023, PhysioMimix data was supplied to supports Inipharm’s INI-822 for metabolic liver disease treatment, which is now in clinical testing. PhysioMimix assay for Metabolic dysfunction-associated steatohepatitis (MASH) was leveraged to confirm efficacy for INI-822. The use of in vitro OOC for early evidence of efficacy for INI-822 demonstrates the transformative potential of these models to provide human-relevant data within preclinical programmes.