Bioreactor Coupling Facility for Dynamic Metabolite Analysis
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Solution Overview
Problem
Current in vitro cellular cultures on Petri dishes fail to maintain long-term viability of primary cells like hepatocytes, lack dynamic fluid circulation, and are unable to perform real-time analysis of xenobiotic metabolism and biomarker detection, especially for unstable or low-concentration metabolites.
Innovation Solution
A coupling facility is developed that connects a bioreactor in dynamic mode to a physicochemical analysis unit with a closed perfusion loop, including a sample loop, six-way valves, and a cleaning loop, allowing for real-time and continuous analysis, sample trapping, and easy cleaning without contaminating the samples.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If a bioreactor with closed perfusion loop is used, then continuous real-time analysis is enabled, but device complexity increases
Solution Approach 1:
The system is divided into distinct functional modules: bioreactor unit, perfusion loop with sample loop, valve system, and analysis unit. This segmentation allows continuous operation while managing complexity through modular design, where each component performs a specific function and can be independently maintained or replaced.
Solution Approach 2:
A six-way valve system acts as an intermediary between the perfusion loop and the analysis unit, enabling multiple functions (sampling, cleaning, eluent delivery) through a single component. This mediator allows the system to switch between different operational modes without requiring separate pathways for each function.
2Reliability
If frequent cleaning of the analysis unit is performed, then signal loss due to fouling is prevented, but sample contamination risk increases
Solution Approach 1:
A dedicated cleaning loop is extracted from the main perfusion circuit, allowing cleaning solutions to be circulated through the analysis unit without contacting the biological samples in the bioreactor. This separate pathway enables frequent cleaning while preventing cross-contamination between cleaning agents and samples.
Solution Approach 2:
The six-way valve system serves as an intermediary that directs cleaning solutions through the analysis unit while isolating the sample loop and bioreactor. The valves control the flow paths to ensure cleaning agents never mix with biological samples, maintaining both reliability and sample integrity.
3Measurement precision
If dynamic mode with fluid circulation is used, then real behavior of irrigated tissue is reproduced, but cell viability duration decreases
Solution Approach 1:
The system implements periodic sampling and analysis cycles rather than continuous withdrawal of culture medium. The bioreactor maintains dynamic fluid circulation to reproduce physiological conditions, while periodic analysis through the sample loop allows monitoring without disrupting the culture environment or removing essential nutrients.
Solution Approach 2:
The closed perfusion loop maintains continuous fluid circulation and nutrient supply to the cells, ensuring long-term viability. The sample loop enables continuous monitoring capability by continuously circulating a portion of the medium through the analysis unit without removing it from the system, thus maintaining both physiological relevance and extended culture duration.
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 continuous and precise analysis of metabolites and biomarkers, prevents signal loss due to fouling, and allows for easy transport and use, maintaining dynamic culture conditions and enhancing the detection of transient cellular processes.
Implementation Method 1
The notion of 'dynamic mode' means that the fluid in which the culture bathes is circulated by a pump
Implementation Method 2
a first valve (3) comprising six ways, and a second valve (4) comprising six ways
Implementation Method 3
the unit being equipped with a pump (20) and an injector (21)
Implementation Method 4
a coupling facility between this culturing bioreactor in dynamic mode and at least one physicochemical analysis unit, such as a liquid chromatography device
Data Source
AI summary
The invention concerns a facility for coupling a bioreactor for culturing bio-organisms, in dynamic mode, with at least one device for physicochemically analyzing a fluid from this bioreactor or collecting samples of this fluid, the device being equipped with a pump and an injector, the bioreactor being equipped with means for supplying culture medium and xenobiotic(s). The facility is remarkable in that the bioreactor is connected to a closed perfusion loop provided with a pump, fitted with a sampling loop and in that the facility comprises:a device for injecting a cleaning product into said sampling loop,two six-way valves, the first valve being connected to the closed perfusion loop, to the sampling loop and to a cleaning loop, the second valve being connected to the cleaning loop and an injection loop that connects the injector to at least one of the devices.