Extra-capillary fluid cycling system and method for a cell culture device
Inventors
Page, Darrell Paul • Wojciechowski, Robert J. • Crep, Martin Peder
Assignees
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Publication Number
US-11345882-B2
Publication Date
2022-05-31
Expiration Date
Abstract
An extra-capillary fluid cycling unit for maintaining and cycling fluid volumes in a cell culture chamber includes a housing and a first flexible reservoir extra-capillary fluid reservoir disposed in the housing. The extra-capillary fluid reservoir is in fluid communication with a cell culture chamber. A second flexible reservoir is also located in the housing, the second flexible reservoir being in fluid communication with a pressure source. A sensor plate is movably disposed in the housing between the extra-capillary reservoir and the second reservoir, wherein the second reservoir is pressurized to move the sensor plate in relation to the extra-capillary reservoir to cause fluid cycling and maintain fluid volumes in the cell growth chamber.
Core Innovation
The invention provides an integrated extra-capillary (EC) fluid cycling unit for a disposable hollow-fiber bioreactor cell culture system. The system maintains and cycles fluid volumes within a cell culture chamber by using an EC fluid reservoir that is flexible and non-rigid, positioned in fluid communication with the bioreactor. Fluid volume changes are generated by converting pressurization into reservoir expansion and contraction in a controlled manner.
The cycling unit includes a housing with rigid walls and a flexible fluid reservoir movably disposed within the housing. A movable mechanical force apparatus acts on a single plate positioned between the flexible fluid reservoir and the mechanical force apparatus. Movement of the single plate relative to the flexible fluid reservoir causes fluid cycling and maintains fluid volumes, while maximum expansion of the flexible reservoir is restricted by a rigid side wall of the housing.
A sensor indicator is connected to the single plate, such that physical expansion and contraction of the flexible reservoir moves the sensor indicator within the housing. The position of the sensor indicator is sensed by a sensor, which is in communication with the mechanical force apparatus when the cultureware module is installed on an instrumentation base device. This sensing controls the force applied by the mechanical force apparatus to the flexible fluid reservoir, thereby cycling EC fluid while operating as a sealed/disposable closed system.
The integrated design is associated with a cultureware module that encloses both the cell culture chamber and the fluid cycling unit within a casing, and includes integrated interface features that align and mate with an instrumentation base device for mechanical and electrical interfaces. The document further describes installation on a reusable instrumentation base device with a disposable cultureware module, including fluid level measurement using sensing rather than ultrasonics or load cells.
Claims Coverage
The identified independent claim is directed to a cultureware module that integrates a cell culture chamber with a fluid cycling unit, where a flexible fluid reservoir is mechanically cycled under sensor-controlled force when the module is installed on an instrumentation base device. The independent claim includes four inventive features.
Sensor-controlled mechanical force cycling using movable single plate and flexible reservoir
A housing encloses a cell growth chamber and a fluid cycling unit, where a flexible fluid reservoir is movably disposed in the housing in fluid communication with the cell growth chamber, and a mechanical force apparatus moves against a single plate to contact the flexible fluid reservoir, thereby applying force through the single plate to cause fluid cycling and maintain fluid volumes.
Sensor indicator positioned by reservoir expansion/contraction
A sensor indicator connected to the single plate is moved within the housing by physical expansion and contraction of the flexible fluid reservoir, such that the position of the sensor indicator can be sensed by a sensor, wherein the sensor communicates with the mechanical force apparatus when the cultureware module is installed on the instrumentation base device to control the force applied to the flexible fluid reservoir through the single plate.
Rigid-walled housing restricting maximum reservoir expansion
The flexible fluid reservoir and the mechanical force apparatus are surrounded by rigid walls of the housing, and maximum physical expansion of the flexible fluid reservoir is restricted by a rigid side wall of the housing.
Integrated interface features for mechanical and electrical mating with instrumentation base device
Integrated interface features align and mate with interface features on an instrumentation base device when the cultureware module is installed, allowing for mechanical and electrical interfaces between the cultureware module and the instrumentation base device.
Across the independent claim, fluid cycling is achieved using a movable mechanical force apparatus acting on a single plate and a flexible fluid reservoir inside a rigid-walled housing. A sensor indicator tracks physical expansion and contraction and, when installed on an instrumentation base device, enables control of applied force to maintain cycling of fluid volumes in the cell growth chamber via sensed position.
Stated Advantages
Accurate fluid level control without ultrasonics/load cells.
Reduced fouling from cell debris.
Lower-cost disposable flexible reservoirs.
Contamination-limiting sealed EC reservoir operation.
Documented Applications
Disposable hollow-fiber bioreactor cell culture systems using an integrated extra-capillary (EC) fluid cycling unit for maintaining and cycling fluid volumes in a sealed disposable/closed system context.
Operation of a transmembrane perfusion loop in cell culture with intracapillary (IC) space and extracapillary (EC) space, using sensing to control cycling of EC fluid volumes.
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