Gut on a chip

Use case

Intestinal cell coculture under flow to replicate gut physiology

Talk to an expert

Gut-on-a-chip

Complete microfluidic setup included for quick and easy assembly.

Dynamic culture conditions

Precisely controlled shear stress under laminar flow, ensuring efficient medium distribution.

Advanced in vitro / ex vivo

Optimized incubation parameters closely mimic physiological conditions for more accurate results.

Highlights

Microfluidic gut-on-a-chip overview

Gut-on-a-chip systems represent a promising advancement in microfluidics and tissue engineering, offering a more physiologically relevant alternative to traditional 2D cell cultures and animal models for studying gut function. These systems simulate the complex microenvironment of the gastrointestinal tract, including the gut’s structural, immunological, and endocrine roles. They enable precise control over factors like fluid flow, mechanical strain, and oxygen levels, enhancing the study of host-microbiome interactions, disease pathogenesis, and drug responses. Despite challenges in replicating the full spectrum of gut functions and tissue integration, these platforms hold potential for revolutionizing drug testing and personalized medicine. Gut-on-a-chip systems mimic the human intestine’s key structures, featuring two microchannels separated by porous, flexible membranes. These microchannels represent the intestinal lumen and blood vessels, lined with gut epithelial and vascular endothelial cells, respectively. Fluid flow simulates the gut’s dynamic environment, promoting realistic tissue behavior [1]. PDMS is the most common material used for its gas permeability, optical transparency, and biocompatibility, though it may adsorb lipophilic compounds. The power of precision of the OB1 and Elveflow complete range of products paired with these specific microfluidic chips can help establish cocultures of intestinal endothelial and epithelial cells.

Figure 1: Features and components of gut-on-a-chip systems [2]

Recent trends

Recent advancements in gut-on-a-chip (GoC) systems are driving a transformative approach to studying human intestinal biology. These systems integrate sophisticated microfluidic technology to simulate the complex physiological and mechanical conditions of the human gut. They replicate essential features such as the intestinal barrier, fluid flow, peristalsis, and cell differentiation within a three-dimensional (3D) environment, overcoming the limitations of traditional two-dimensional (2D) cultures and animal models. As a result, GoC platforms have become invaluable in research areas like drug testing, disease modeling, microbiome interactions, and the development of personalized medical treatments.

Organ-on-chip experiments can be complex, but with our extensive experience from collaborating on numerous projects, we’re here to help. We value the opportunity to share our knowledge and discuss your specific research needs. Our setup is flexible, to be customized with additional instruments tailored to your specific requirements. It’s also compatible with other commercially available or custom-made microfluidic chips.

Setup

Gut-on-a-chip Experimental setup

This setup is designed to replicate realistic shear stress variations, pressure, and strain, closely mimicking the physiological environment of the gut.

The system ensures excellent compatibility among all components, allowing you to begin your experiments right out of the box. Managed by a single software platform, this versatile setup can also be adapted for various applications beyond gut-on-a-chip research. It could offers everything you need to create a dynamic and physiologically relevant gut-on-a-chip model, adaptable to your specific research needs.

Gut-on-a-chip experimental setup components:

Benifits of Elveflow equipments for the Experiment:

OB1 Pressure controller:

- Precise fluid and gas flow control: Its high precision ensures that the fluids within the gut-on-a-chip device closely mimic the natural conditions of the human intestine.
- Customization: The OB1 system is customizable, offering up to four independent pressure or vacuum channels. This flexibility allows researchers to design complex flow patterns and apply different pressures to various sections of the gut-on-a-chip device, facilitating the study of diverse physiological conditions.

MUX Recirculation:

- Continuous fluid flow: In the human gut, nutrients and other substances flow consistently in one direction. The MUX Recirculation valve enables a similar unidirectional flow within the microfluidic chip, ensuring that the medium (containing nutrients and other necessary components) circulates steadily.
- Stable experimental conditions: By facilitating closed-loop recirculation, the MUX Recirculation valve helps maintain consistent concentrations of nutrients and other factors within the chip. This stability is essential for long-term experiments, allowing researchers to observe cellular behaviors and interactions over extended periods without significant fluctuations in the experimental environment.

MUX Distribution:

- Automation and versatility: This rotary valve enables the distribution of different media to various channels within the gut-on-a-chip device or the collection of samples from different channels for analysis.

Application

Disease Modeling and Drug Testing

One of the most significant trends in GoC technology is its application in disease modeling. Traditional models have struggled to replicate the intricate architecture and diverse cell types found in the human gut, limiting insights into the pathogenesis of gastrointestinal disorders. In contrast, GoC systems successfully model conditions such as inflammatory bowel disease (IBD), colorectal cancer, and intestinal infections. By reproducing the gut’s microenvironment, researchers can study how disease states alter tissue structure and function in unprecedented detail. For instance, GoC devices have been used to mimic the inflammatory processes seen in IBD, facilitating the investigation of immune responses, epithelial barrier disruption, and tissue remodeling. Drug testing is another area where GoC platforms are revolutionizing research. These systems provide a human-relevant model to study drug absorption, metabolism, and toxicity. By incorporating patient-derived cells, GoC devices allow researchers to explore personalized drug responses, tailoring treatments to individual genetic and physiological profiles. This represents a promising step towards personalized medicine, especially for gastrointestinal and systemic diseases. Furthermore, by simulating drug metabolism and intestinal permeability, GoC systems provide a valuable tool for evaluating the efficacy and safety of pharmaceuticals before clinical trials, addressing the inadequacies of animal models that often fail to predict human outcomes.

Host-Pathogen interaction

Advancements in gut-on-a-chip (GoC) technology have significantly enhanced the understanding of pathogen-host interactions within the gastrointestinal tract. By integrating 4D live imaging with GoC systems, researchers can observe real-time pathogen invasion under conditions that closely mimic the human gut’s mechanical environment, including peristaltic movements. This approach has been instrumental in studying pathogens like Entamoeba histolytica and Shigella flexneri, providing detailed insights into their invasion mechanisms and the resulting host tissue responses. Such studies are crucial for developing targeted therapies and preventive measures against gastrointestinal infections. (discover the full story here)

Host-Microbiome Interactions

The gut microbiome plays a critical role in human health, impacting digestion, immune function, and the progression of various diseases. However, studying the microbiome’s influence in vitro has been challenging due to the difficulties of recreating a physiologically relevant and controlled environment. Recent GoC innovations have focused on incorporating live, anaerobic microbiota into these platforms. This allows the simultaneous study of microbial communities and host tissues, revealing the effects of microbial metabolites and the impact of dysbiosis on gut health. These systems have enabled the investigation of how beneficial bacteria, like probiotics, modulate epithelial function and pathogen defense, providing a novel method for exploring therapeutic strategies.

Figure 4: Gut-microbiota-on-a-chip device with a porous ECM-coated membrane lined by gut epithelial cells [1,4]

Gut-Immune System Interactions

The integration of immune components within GoC systems marks a significant leap in understanding gut-immune crosstalk. The gut is a crucial site of immune regulation, interacting with both resident microbes and circulating immune cells. GoC models incorporating immune cells, such as macrophages or peripheral blood mononuclear cells (PBMCs), facilitate the study of immune responses under near-physiological conditions. This is especially valuable for researching inflammatory diseases and the gut’s role in systemic immune activation.

Figure 5: Gut-on-a-chip microfluidic device for investigation of contributions of the microbiome and mechanical deformation to intestinal bacterial overgrowth and inflammation. Probiotic VSL#3 protect against EIEC-induced, immune cell-associated intestinal injury on-chip. [5]

Gut-Organ-Axis on Chip

An exciting trend in GoC research is the integration of gut models into multi-organ-on-a-chip (MoC) systems. These platforms connect the gut with other organ models, such as the liver, kidney, or brain, to study systemic interactions. This is particularly useful for exploring the first-pass metabolism of orally administered drugs, where compounds are absorbed through the intestinal wall and processed by the liver before entering systemic circulation.

Gut-Brain Axis on Chip

Research has confirmed that the brain and gut communicate directly through the gut-brain axis (GBA) [6], suggesting that the gut environment can influence the brain’s neurocognitive functions. Gut health is linked to neurodegenerative diseases like Alzheimer’s and Parkinson’s. Multi-organ-on-a-chip (multi-OOC) models help study the brain–gut-immune axis interactions. The gut and brain communicate via microbial metabolites crossing the gut epithelium and blood-brain barrier (BBB), which protect against harmful substances while maintaining balance and stability.

Gut-Liver Axis on Chip

Intestinal and hepatic microphysiological systems model gut-liver axis interactions [7], exploring how gut-liver communication affects metabolism and immune responses. The intestine and liver process substances through complex pathways, impacting drug efficacy and nutrient absorption. Traditional models such as animal models or static tissue cultures struggle to replicate this, but GBA microarrays offer a solution for more accurate studies.

Figure 6: GLA-On-Chip [7]

References

Y. Guo ; X. Chen ; P. Gong ; G. Li, W. Yao and W. Yang, The Gut–Organ-Axis Concept: Advances the Application of Gut-on-Chip Technology, International Journal of Molecular Sciences, 2023
N. Ashammakhi ; R. Nasiri ; NR. De Barros ; P. Tebon ; J. Thakor ; M. Goudie ; A. Shamloo ; MG. Martin and A. Khademhosseni, Gut-on-a-chip: Current progress and future opportunities, Biomaterials, 2020
A. Boquet-Pujadas et al., “4D live imaging and computational modeling of a functional gut-on-a-chip evaluate how peristalsis facilitates enteric pathogen invasion,” 2022. [Online]. Available: https://www.science.org//
H.J. Kim, D. Huh, G. Hamilton, D.E. Ingber, Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow, Lab Chip, 2012
H.J. Kim, H. Li, J.J. Collins, D.E. Ingber, Contributions of microbiome and mechanical deformation to intestinal bacterial overgrowth and inflammation in a human gut-on-a-chip, Proc Natl Acad Sci U S A, 2016
Kim, M.-H.; Kim, D.; Sung, J.H. A Gut-Brain Axis-on-a-Chip for studying transport across epithelial and endothelial barriers. J.Ind. Eng. Chem. 2021.
Chen, H.J.; Miller, P.; Shuler, M.L. A pumpless body-on-a-chip model using a primary culture of human intestinal cells and a 3D culture of liver cells. Lab A Chip 2018

Gut on a chip

Use case

Intestinal cell coculture under flow to replicate gut physiology

Talk to an expert

Gut-on-a-chip

Powerful & complete microfluidic setup.

Dynamic culture conditions

Precisely controlled shear stress under laminar flow, ensuring efficient medium distribution.

Advanced in vitro / ex vivo

Optimized incubation parameters closely mimic physiological conditions for more accurate results.

Talk to an expert

Gut on a chip

Use case

Gut-on-a-chip

Dynamic culture conditions

Advanced in vitro / ex vivo

Microfluidic gut-on-a-chip overview

Recent trends

Gut-on-a-chip Experimental setup

Gut-on-a-chip experimental setup components:

Benifits of Elveflow equipments for the Experiment:

OB1 Pressure controller:

MUX Recirculation:

MUX Distribution:

Disease Modeling and Drug Testing

Host-Pathogen interaction

Host-Microbiome Interactions

Gut-Immune System Interactions

Gut-Organ-Axis on Chip

Gut-Brain Axis on Chip

Gut-Liver Axis on Chip

Gut on a chip

Use case

Gut-on-a-chip

Dynamic culture conditions

Advanced in vitro / ex vivo

Features & Benefits

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