Organ-on-chip free-surface oxygenator for low-volume cell culture
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Solution Overview
Problem
Existing organ-on-chip platforms face challenges in efficiently oxygenating cells at low circulating fluid volumes due to surface tension effects, leading to inefficient oxygenation and potential cell dehydration, which hinders the operation of microfluidic devices used in drug development and tissue culture.
Innovation Solution
The development of organ-on-chip platforms with volume-limited free-surface oxygenators and fluid circulation configurations that maintain a defined fluid path, incorporating spiral surface geometries to constrain fluid and reduce diffusion depth, and attachment means for securing scaffolds to prevent fluid bypassing, allowing efficient oxygenation and culture of cells at reduced fluid volumes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If the circulating fluid volume is reduced in organ-on-chip platforms, then the dilution effect is minimized and biomarker detection is improved, but surface tension effects dominate and prevent efficient oxygenation
Solution Approach 1:
The patent introduces a vertical dimension by creating a free-surface oxygenator where fluid forms a meniscus at the air-liquid interface. This dimensional change allows oxygenation to occur at the surface rather than requiring bulk fluid circulation, enabling low-volume operation while maintaining efficient oxygen transfer.
Solution Approach 2:
The oxygenator channel is segmented into a narrow width (100-500 μm) to create a defined free surface. This segmentation allows the fluid to form a stable meniscus at the air interface, enabling oxygenation without requiring large circulating volumes.
2Area of stationary object
If a wide channel is used for oxygenation, then sufficient surface area is provided for oxygen mass transfer, but fluid accumulates in the oxygenator and cells run dry
Solution Approach 1:
The oxygenator channel has different width characteristics at different locations: narrow (100-500 μm) at the oxygenation section to create free surface, and wider elsewhere to allow fluid accumulation without depleting cell culture volume. This local quality variation resolves the contradiction between oxygenation area and fluid retention.
3Reliability
If bidirectional flow is implemented in the oxygenation tail, then oxygenation efficiency is improved, but fluid volume requirements increase
Solution Approach 1:
The free-surface oxygenator design allows oxygenation to occur passively at the air-liquid interface without requiring active bidirectional pumping. The narrow channel geometry and surface tension effects naturally maintain the free surface, enabling oxygenation with unidirectional or low-volume flow.
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
These platforms enable effective oxygenation and culture of cells at circulating volumes as low as 50 μL to 1000 μL, ensuring reliable oxygen supply and preventing cell dehydration, thereby enhancing the efficiency and accuracy of drug development and tissue culture processes.
Implementation Method 1
The main challenge with reducing volume in an open well format is the dominance of surface tension at small length-scales. Simply putting less medium in the LIVERCHIP® platforms causes the fluid to wet the corners of the oxygenator channels
Implementation Method 2
liquid media is oxygenated in a long, wide channel to provide enough free-surface area for adequate oxygen mass transfer
Data Source
AI summary
Organ-on-chip platforms with reduced fluid volumes include circulating fluid volumes of below 1000 μL, preferably about 500 μL or less. The platforms are adjustable for culturing cells with varied oxygen demand at various seeding densities. The platforms include at least one lane, wherein each lane includes at least one cell culture well, at least one oxygenator for fluid oxygenation, and a pump system containing at least one pump per lane. The oxygenator may include a separate fluid path for oxygenating the fluid, which allows controlling and measuring the oxygen concentration in the fluid, shortening the diffusion length, and passively diffusing oxygen. Provided are also different configurations for the oxygenator, fluid circulation in the platforms, attachment means for securing scaffolds to culture wells, and pneumatic plates.