In Vitro Gastrointestinal Model with Artificial Mucosal Layer
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current in vitro gastrointestinal models lack the ability to simulate host responses and feedback mechanisms, such as hormonal and neural control, and do not account for the resident microbial community of the small intestine, limiting their relevance to in vivo conditions and effectiveness in evaluating nutritional candidates and gut health interventions.
Innovation Solution
An in vitro model of the gastrointestinal tract is developed, comprising multiple fermentation vessels simulating the duodenum, jejunum, and ileum with specific microorganisms and conditions, along with a large intestine model, to mimic the physiological processes of the small and large intestines, including nutrient absorption and microbial metabolism, using a multi-stage system with controlled pH and anaerobic conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If current in vitro gastrointestinal models are used, then the system complexity is reduced and ease of operation is improved, but the ability to simulate host responses and feedback mechanisms is lost, reducing measurement precision
Solution Approach 1:
The patent introduces an artificial mucosal layer as an intermediary component between the microbial community and the external environment. This layer acts as a mediator that simulates host epithelial cell functions, enabling the model to capture host responses and feedback mechanisms while maintaining the simplicity of an in vitro system. The mucosal layer serves as a bridge that translates microbial activities into host-relevant outcomes without requiring complex living host tissues.
Solution Approach 2:
The patent creates a simplified copy of the host mucosal barrier using artificial materials and structures that replicate the essential functions of the intestinal epithelium. Rather than using complex living host tissues, the model employs a copied representation that captures the key protective and selective properties of the mucosal layer, enabling measurement of host responses in a simplified in vitro context.
2Reliability
If complex in vitro models like SHIME and TNO Intestinal Models are used, then the ability to simulate digestive processes is improved, but the device complexity increases and small intestine microbiota are still not accounted for
Solution Approach 1:
The patent extracts and isolates the specific function of the small intestine mucosal barrier from the complex whole-system models. Rather than attempting to replicate entire digestive tracts with multiple chambers and processes, the invention focuses on extracting the essential mucosal interface function and implementing it in a simplified configuration that can be integrated into existing models or used independently.
Solution Approach 2:
The patent segments the gastrointestinal model into distinct functional components, with the artificial mucosal layer representing a specific segment (the host-microbe interface). This segmentation allows the complex system to be broken down into manageable modules, where each component performs a specific function, reducing overall device complexity while maintaining reliability through modular design.
3Reliability
If 3D co-culture microfluidic models are used, then the ability to model host-cell interactions is improved, but the models cannot support metabolically-active bacteria within a full complex microbial community due to oxygen exposure
Solution Approach 1:
The patent implements an anaerobic (inert) atmosphere within the model system to support metabolically-active bacteria. By creating an oxygen-free environment using appropriate gas phases and sealed configurations, the model can accommodate a full complex microbial community including obligate anaerobes, while still maintaining host cell viability through controlled nutrient supply and waste removal mechanisms.
Solution Approach 2:
The patent designs a multi-functional system that simultaneously supports both aerobic host cells and anaerobic bacteria. The model incorporates multiple functional capabilities: oxygen supply for eukaryotic cells, anaerobic conditions for bacteria, nutrient delivery, waste removal, and pH control. This universality allows a single system to accommodate diverse biological requirements without compromising the reliability of either component.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This model enables cost-effective screening of nutritional candidates for microbiome supplementation and modulation, enhances the understanding of nutrient digestion and bioavailability, and provides a more accurate representation of the interplay between small and large intestine microbiomes, improving the characterization of dietary inputs and their effects on gut health.
Implementation Method 1
an in vitro model of an in vivo small intestine including a plurality of fermentation vessels... an in vitro model of an in vivo large intestine including a plurality of fermentation vessels
Implementation Method 2
A few models have attempted to mimic the peristaltic mixing of chyme in the small and large bowel
Data Source
AI summary
An in vitro model of an in vivo gastrointestinal tract including an in vitro model of an in vivo small intestine including a plurality of fermentation vessels and an in vitro model of an in vivo large intestine including a plurality of fermentation vessels is provided. A method of simulating a biotransformation of food product through the human digestive tract using an in vitro model of an in vivo gastrointestinal tract is provided.