Bioreactor Closed-Loop System for 3D Cell Culture
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Solution Overview
Problem
Current microfluidic biochips are limited by their small volume, restricting them to two-dimensional cell cultures and lacking flexibility, which hinders the simulation of complex biological circulatory systems and microenvironments.
Innovation Solution
A bioreactor apparatus with a closed-loop system comprising a liquid storage chamber, pump, and multiple interconnected culture chambers, allowing for three-dimensional cell culture and adjustable microenvironment simulation, enabling the cultivation of different cells and organoids with controlled medium flow and ingredient concentration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If microfluidic biochip is used for cell culture, then sample volume is reduced, but cultural space is limited and three-dimensional culture is not supported
Solution Approach 1:
The bioreactor is divided into multiple independent culture chambers (first culture chamber, second culture chamber, etc.) that can be separately configured. Each chamber can accommodate different cell types or organoids, allowing the system to achieve three-dimensional culture while maintaining small individual sample volumes in each chamber.
Solution Approach 2:
The patent transitions from two-dimensional microfluidic chip culture to three-dimensional culture by introducing vertical stacking of multiple culture chambers. The first culture chamber and second culture chamber are arranged in vertical succession, enabling three-dimensional spatial utilization for cell culture while maintaining controlled sample volumes in each chamber.
2Manufacturing precision
If microfluidic biochip patterns are prefabricated by precision instrument, then manufacturing precision is improved, but flexibility for adjustment is reduced
Solution Approach 1:
The bioreactor design allows dynamic adjustment of culture chamber configurations, medium flow rates, and ingredient concentrations after the system is assembled. The modular structure enables flexible reconfiguration of multiple culture chambers to match different experimental needs, overcoming the rigidity of prefabricated microfluidic patterns.
Solution Approach 2:
By segmenting the bioreactor into multiple independent culture chambers with separate inlet and outlet channels, the system allows flexible adjustment of each chamber's operating conditions independently. This modular segmentation provides adaptability for different cell types and experimental requirements while maintaining precise manufacturing of each individual chamber.
3Device complexity
If microfluidic biochip is used, then device complexity is reduced, but ability to simulate biological circulatory system is limited
Solution Approach 1:
The bioreactor divides the circulatory system simulation into multiple segmented culture chambers, each representing different tissue or organ regions. The first culture chamber, second culture chamber, and their interconnected medium channels mimic the segmented nature of biological circulatory systems, enabling complex physiological simulations while keeping individual chamber structures relatively simple.
Solution Approach 2:
The patent merges multiple culture chambers with shared medium storage and circulation systems to create an integrated bioreactor that can simulate the biological circulatory system. The combination of multiple chambers with common inlet/outlet channels and medium flow control enables complex system-level simulations while avoiding the need for an entirely complex monolithic structure.
4Reliability
If culture medium flow is increased to improve nutrient supply, then cell viability is improved, but system complexity and energy consumption increase
Solution Approach 1:
The bioreactor employs continuous circulation of culture medium through the first culture chamber and second culture chamber via closed-loop channels. The pump maintains continuous flow to ensure constant nutrient supply and waste removal, improving cell viability while using simple continuous flow control rather than complex intermittent systems.
Solution Approach 2:
The culture medium serves multiple functions simultaneously: it provides nutrients to cells, removes waste products, transports gases (oxygen and carbon dioxide), and enables communication between different culture chambers through the shared circulation system. This multi-functionality reduces the need for separate systems to achieve each objective, simplifying overall device complexity.
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
The bioreactor system effectively simulates biological circulatory systems and microenvironments, enabling the cultivation of various cells and organoids with high viability, and allows for flexible adjustments and additions, enhancing applications like drug screening and environment testing.
Implementation Method 1
the pump is configured to provide pressure for driving the flow of the culture medium within the closed loop
Data Source
AI summary
Provided is a bioreactor apparatus including: a liquid storage chamber for storing a culture medium; a pump for providing pressure to drive the flow of the culture medium; a plurality of culture chambers providing an accommodating space to accommodate the culture medium and a cell to be cultured; and a pipeline connecting the liquid storage chamber, the pump, and the culture chamber to form a closed loop. Also provided is a bioreactor system including the bioreactor apparatus of the present disclosure, the culture medium, and a cell. Further provided is a method for culturing a cell or an organoid by the bioreactor apparatus of the present disclosure. The bioreactor apparatus, bioreactor system, and method of the present disclosure can form a biomimetic circulatory system, which is beneficial for simulating and evaluating the complex microenvironment and physiological mechanism in the living body.