Perfusion Bioreactor with Filtered Flow for 3D Cell Culture
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Solution Overview
Problem
Current 3D cell culture techniques face limitations such as restricted cell migration, defined cell environments, time inefficiency, lack of optical access for microscopy, and limited cell viability due to passive support mediums that cannot efficiently expel cellular waste, leading to cytotoxic environments.
Innovation Solution
A bioreactor system with active perfusive flow through a porous support medium, allowing continuous optical access, using a 3D cell growth medium with hydrogel particles and a liquid cell culture medium, and a system comprising a sample well, a medium reservoir, and a collection chamber connected by filters, enabling fluid perfusion and waste removal.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If passive 3D support medium is used for cell culture, then cell migration is limited, but cell viability is reduced due to inability to expel waste efficiently
Solution Approach 1:
The patent applies hydraulic principles by implementing an active perfusion system that pumps culture medium through the 3D cell culture insert. This creates controlled fluid flow that continuously removes cellular waste products while delivering nutrients, resolving the contradiction between maintaining cell viability and preventing waste accumulation. The perfusion system transforms the static passive support medium into a dynamic system with controlled hydraulic flow.
2Stability of the object's composition
If polymer scaffold is used to define cell environment, then cell morphology is maintained, but cell migration is limited or precluded
Solution Approach 1:
The patent employs a porous membrane support medium that provides structural stability to maintain cell environment while allowing cell migration through its porous structure. The pores enable cells to move freely while the membrane provides mechanical support and defines the culture environment, thus resolving the contradiction between environment stability and migration capability.
Solution Approach 2:
The patent applies local quality by creating distinct regions with different properties: the porous membrane provides structural support where needed while maintaining open spaces that allow cell migration. The perfusion system also creates local flow patterns that can be optimized for different regions of the culture insert, enabling both environmental stability and cell mobility in different locations.
3Duration of action of stationary object
If existing 3D culture method is used, then initial setup is completed, but cell viability is limited to several days due to waste accumulation
Solution Approach 1:
The patent implements continuous perfusion flow that constantly refreshes the culture medium and removes waste products throughout the cell culture period. This continuous action prevents the buildup of cytotoxic substances and maintains favorable culture conditions for extended periods, extending cell viability from several days to much longer durations.
Solution Approach 2:
The perfusion system enables feedback control by allowing monitoring of culture conditions and adjusting flow rates accordingly. This ensures that waste removal keeps pace with cellular metabolism, preventing cytotoxic environment development and extending viable culture duration.
4Ease of manufacture
If conventional 3D cell culture technique is used, then cells are seeded on polymer scaffold, but optical access for microscopy is not provided
Solution Approach 1:
The patent uses thin film membrane supports that provide structural integrity while being optically transparent. These thin films allow light to pass through for microscopy observation while maintaining the necessary mechanical support for 3D cell culture, thus resolving the contradiction between manufacturing simplicity and optical accessibility.
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 system enables long-term 3D growth of biological samples with continuous optical access, improving cell viability and allowing for efficient waste removal, thus overcoming the limitations of existing methods.
Implementation Method 1
a first filter material... fluidly connected to the sample well... draws fluid from the liquid medium reservoir, through the first filter material, into the sample well
Implementation Method 2
permeates the three-dimensional cell growth medium... application of negative gage pressure to the medium collection chamber or positive pressure to the liquid medium reservoir draws fluid
Data Source
AI summary
Disclosed herein is a bioreactor system that allows active perfusive flow through a porous support medium enabling 3D growth of biological samples. In some embodiments, the system comprises a sample well filled with a three-dimensional (3D) cell growth medium. The system can further comprise a liquid medium reservoir fluidly connected to the sample well by a first filter material. The system can further comprises a medium collection chamber fluidly connected to the sample well by a second filter material. In some embodiments, application of negative gage pressure to the medium collection chamber or positive pressure to the liquid medium reservoir draws fluid from the liquid medium reservoir, through the first filter material, into the sample well where it permeates the three-dimensional cell growth medium, through the second filter material, and finally into the medium collection chamber.