Pellets for Cell Culture Media via Fluid Bed Pelletization
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Solution Overview
Problem
Current methods for producing pelletized cell culture media face challenges in maintaining cell viability and growth due to the complexity of formulations, which often result in undesirable properties like stickiness and poor flow, making it difficult to achieve effective pelletization and sustain cell performance.
Innovation Solution
A method involving fluid bed pelletization using a rotor disc technology to form pellets from a mixture of amino acids, sugars, vitamins, and salts, with controlled binder and excipient composition, and varying particle sizes to optimize pellet characteristics for improved cell culture media.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If complex formulations are used to support cell cultivation, then cell growth and protein production are enhanced, but the mixture exhibits undesirable properties like stickiness and poor flow
Solution Approach 1:
The complex cell culture formulation is segmented into multiple dry powder components that are separately prepared and then combined through fluid bed pelletization. This segmentation allows each component to maintain its own optimal properties while being integrated into a unified pellet structure, avoiding the stickiness that would result from mixing all components together in liquid form.
Solution Approach 2:
The formulation parameters are changed from liquid state to dry powder state. By converting the complex formulation into dry powders with controlled particle size distributions and using controlled binder addition during pelletization, the mixture maintains cell viability while achieving desirable flow properties and eliminating stickiness.
2Reliability
If dry powder is used for cell culture media, then storage and handling are improved, but pelletization is difficult due to poor flow and stickiness
Solution Approach 1:
The pelletization process uses dynamic control of binder addition and fluid bed parameters. The binder is added in a controlled manner during the pelletization process, and the fluid bed parameters are dynamically adjusted to maintain optimal conditions for pellet formation, allowing dry powder with poor initial flow to be transformed into well-formed pellets.
Solution Approach 2:
A controlled binder acts as an intermediary substance during pelletization. The binder is added in precise amounts to facilitate particle aggregation without causing excessive stickiness, enabling the transformation of difficult-to-pelletize dry powders into well-formed pellets while maintaining the dry powder stability benefits.
3Reliability
If pelletization is achieved with complex formulations, then cell viability is maintained, but uniform particle size and flowability are difficult to achieve
Solution Approach 1:
The dry powder components are pre-prepared with controlled particle size distributions before pelletization. This preliminary sizing ensures that the starting materials have optimal characteristics for uniform pellet formation, and the process is designed to maintain this uniformity while preserving cell viability through controlled binder addition.
Solution Approach 2:
The pelletization process incorporates feedback control of binder addition and process parameters. By monitoring pellet formation in real-time and adjusting binder addition rates and fluid bed parameters accordingly, the process maintains uniform particle size while ensuring cell viability is preserved throughout the transformation.
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 method produces pellets that maintain cell viability and growth, offering improved physical and chemical properties, such as uniform size and flowability, and enhances protein production, demonstrating effective cell culture performance comparable to liquid media.
Implementation Method 1
subjecting a first dry powder to suspension in an upwardly moving column of a gas in a fluid bed apparatus
Implementation Method 2
spinning in a disc rotor
Implementation Method 3
the first dry powder, the second dry powder, or the solvent comprises a binder, an excipient, or both
Implementation Method 4
drying the pellet
Data Source
Figure 1A
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Figure 1C
AI summary
The present invention is directed generally to dry cell culture media or feeds in pellet formats which can be reconstituted into liquid media for culturing cells in vitro. Each pellet composition may comprise the same or a different composition; for example, different vitamins, amino acids, buffers, trace salts, pH, iron chelators, etc. The invention also relates to methods of making dry cell culture media by altering ratios of different pellet compositions, or, methods of making modular dry cell culture media, or customizing media formulations for growing a cell type using pellets. According to the invention, media pellets may be easier to handle either before reconstitution, during shipping and handling; and/or during reconstitution. Media pellets may be used in any container like bags including sterile, single use bags for preparing media formulations. The invention also relates to kits and culture systems using media pellets.