Removable Sample Portions for Fixed Bed Bioreactor Sampling
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Solution Overview
Problem
Current cell culturing devices, particularly fixed bed bioreactors, face challenges in obtaining accurate and timely samples without disrupting the cell culture environment or risking contamination, as existing methods are cumbersome and lack precise sampling tools.
Innovation Solution
A sampler apparatus is introduced that allows for easy, reliable, and aseptic sampling of fixed bed cell cultures, enabling sampling within or outside a sterile environment, using a structured or unstructured fixed bed with removable sample portions and positioners, and maintaining sterility through connectors and containers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If manual sampling with tweezers is used during fixed bed bioreactor operation, then cell samples can be obtained, but the operation is difficult requiring careful dexterity and causes undesirable perturbations that risk disrupting the cell culture environment
Solution Approach 1:
The fixed bed structure incorporates self-contained sampling ports that allow samples to be accessed directly through the bioreactor wall without requiring manual insertion of tools. The bed material itself provides the sampling interface, eliminating the need for external tweezers and manual manipulation.
Solution Approach 2:
Sampling ports are integrated directly into the fixed bed structure, extracting the sampling function from the bulk bed material. This allows localized access to cell samples without requiring manipulation of the entire bed structure or careful dexterity to navigate within the bioreactor.
2Measurement precision
If manual extraction of bed portions is performed to obtain samples, then cell samples can be obtained, but it invariably causes undesirable perturbations that risk disrupting the cell culture environment and the sample specimen
Solution Approach 1:
Sampling ports are integrated directly into the fixed bed structure, extracting the sampling function from the bulk bed material. This allows localized access to cell samples without requiring manipulation of the entire bed structure or careful dexterity.
Solution Approach 2:
The fixed bed incorporates localized sampling regions with different properties from the bulk bed. These sampling ports provide direct access to cell samples while maintaining the integrity and undisturbed state of the surrounding cell culture environment.
3Reliability
If the bioreactor is placed inside a containment unit such as a laminar flow cabinet or biosafety cabinet to maintain sterile conditions, then sterility is maintained, but the freedom of movement and access of the operator for sampling maneuvers is limited
Solution Approach 1:
The bioreactor system incorporates integrated sampling ports that allow sampling operations to be performed through the reactor wall without requiring the operator to reach inside the containment unit. The system serves itself by providing external access points for sampling.
Solution Approach 2:
Sampling ports act as intermediaries between the sterile internal environment and the non-sterile external environment. These ports allow sample extraction while maintaining the sterile barrier, eliminating the need for operators to physically access the interior of the containment unit.
4Productivity
If sterile liquid sensors are used in a fixed bed bioreactor to assess cell density, then measurements can be obtained, but only information from which an educated guess or estimate can be made regarding cell conditions based on detected byproducts
Solution Approach 1:
The sampling port extracts actual cell material from the fixed bed, allowing direct examination of cells under a microscope. This provides definitive information about cell morphology, density, and health status, replacing indirect sensor-based estimates with direct observation.
Solution Approach 2:
The sampling port provides a physical copy or representation of the actual cell population in the form of extractable cell samples. This allows direct analysis of real cells rather than relying on indirect sensor signals that require interpretation and estimation.
Data Source
AI summary
A sampler for use with a bioreactor for growing a cell culture is disclosed. In one embodiment, the bioreactor includes a structured fixed bed including a removable sample portion for recovering a sample of cells from the cell culture. Related apparatuses and methods are also disclosed.