Perfusion Bioreactor with Segmented Chambers for Stable Host-Microbe Co-Culture
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Solution Overview
Problem
Current bioreactors fail to provide a stable and consistent environment for co-culturing human and bacterial cells, leading to suboptimal growth and interaction, as they often cannot replicate the in vivo conditions necessary for studying human microbiome interactions effectively.
Innovation Solution
A perfusion bioreactor system with multiple chambers allows for the co-culturing of human and bacterial cells in separate environments, enabling continuous mixing of secreted products across membranes to simulate the gastrointestinal tract microbiome, facilitating optimal cell-cell communication and interaction.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If bacteria and human cells are grown in direct contact in co-culture, then cell-cell interaction and communication are enabled, but cellular infection and viability loss occur reducing culture stability
Solution Approach 1:
The bioreactor is divided into two separate chambers (bacterial chamber and human cell chamber) that are physically isolated by a membrane. This segmentation allows each cell type to be cultured in its own optimized environment while still enabling controlled interaction through the membrane, thus maintaining both interaction capability and culture stability.
Solution Approach 2:
A porous membrane serves as an intermediary between the bacterial and human cell chambers. This membrane allows selective passage of molecules (nutrients, secreted products, signals) while preventing direct cell contact that would lead to infection. The intermediary enables indirect communication and interaction without the harmful effects of direct contact.
2Device complexity
If conventional bioreactors are used for co-culture, then device simplicity is maintained, but the ability to replicate in vivo conditions and provide stable nutrition is insufficient
Solution Approach 1:
The bioreactor system is segmented into multiple functional chambers (bacterial chamber, human cell chamber) with separate media reservoirs and perfusion systems. This segmentation allows independent control and optimization of environmental conditions in each chamber, enabling stable replication of in vivo conditions while maintaining a manageable overall structure.
Solution Approach 2:
The bioreactor implements continuous perfusion of culture media through both chambers, mimicking the continuous nutrient supply and waste removal in vivo. This continuous action ensures stable environmental conditions, constant nutrition supply, and effective removal of metabolic byproducts, significantly improving environmental stability compared to batch culture systems.
3Reliability
If separate culture environments are used for bacteria and human cells, then optimal growth conditions for each cell type are maintained, but cell interaction and communication are prevented
Solution Approach 1:
The porous membrane acts as an intermediary that enables molecular communication between the two separate culture environments. It allows passage of nutrients, secreted products, signaling molecules, and metabolites while maintaining physical separation, thus preserving both optimal growth conditions and intercellular communication capabilities.
Solution Approach 2:
A porous membrane with specific pore size is used as the separation barrier between chambers. The porosity allows selective diffusion of molecules based on size, enabling passage of small molecules, peptides, and metabolites while preventing cell passage. This facilitates chemical communication and interaction between cells in separate environments.
4Productivity
If direct co-culture is used to study secreted products, then functional understanding of bacterial products is enabled, but culture duration is limited due to infection
Solution Approach 1:
By segmenting the culture system into separate bacterial and human cell chambers, the invention eliminates the infection problem that limits direct co-culture duration. This allows prolonged culture periods while continuously collecting and analyzing secreted products from both cell types, significantly enhancing research productivity on secreted molecules.
Solution Approach 2:
The membrane intermediary enables long-term co-culture by preventing direct cell contact and infection while allowing continuous exchange of secreted products. This extends culture duration from hours/days in direct co-culture to weeks/months, enabling comprehensive functional analysis of bacterial secreted products and their effects on human cells.
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 setup enables prolonged and stable co-culture of human and bacterial cells, allowing for detailed analysis of secreted signals and interactions, enhancing our understanding of microbiome functions and host-microbe relationships.
Implementation Method 1
a hollow conduit connecting the first and second chambers via an orifice in each of the first and second chambers, wherein the hollow conduit allows fluid communication between the first and second chamber
Implementation Method 2
a first pump in mechanical contact with or in fluid communication with the hollow conduit, the first pump to move fluid between the first chamber and the second chamber
Implementation Method 3
the contents inside or outside the chambers' membranes are continuously mixed with the contents inside or outside of the membrane in a different chamber to expose the environment (or cell population) to the secreted products of the other chamber
Data Source
AI summary
The present invention relates to a perfusion bioreactor for co-culturing, wherein the bioreactor grows cells in two separate environments and enables communication across environments and populations. The chambers' contents are continuously mixed to expose the environment (or cell population) of each chamber to the secreted products of the other chamber. The said bioreactor comprises at least, but not limited to, two chambers, with separate cell populations with at least two separate environments independently selected from aerobic or anaerobic environment and media favorable to cell growth. The bioreactor allows for multiple samples to be collected during an experiment to enable various analytical techniques and results. Additionally, the bioreactor comprises a multi-chamber cell culture system capable of emulating the gastro-intestinal tract.