Permittivity Probe Monitoring of Cell Density in Aggregate Cultures
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Solution Overview
Problem
There is a need for methods to measure cell density in a cell suspension comprising cell aggregates in real time, as existing technologies lack inline measurement capabilities for such systems.
Innovation Solution
The method involves measuring the permittivity of the cell suspension and comparing it with a predetermined value indicative of cell density, using a permittivity probe, to determine cell density in real time.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If offline measurement methods are used to determine cell density, then measurement accuracy can be maintained, but real-time monitoring capability is lost and productivity decreases
Solution Approach 1:
The patent replaces mechanical offline sampling and measurement systems with an optical measurement system that uses light scattering principles. The measurement probe optically detects cell density parameters directly in the bioreactor suspension, eliminating the need for physical sampling, cell dissociation, and offline analysis while providing real-time data for process control
Solution Approach 2:
The patent introduces an optical measurement probe as an intermediary device that indirectly measures cell density by detecting light scattering properties of the cell suspension. This intermediary measurement method enables real-time monitoring without directly interfering with the cell culture process or requiring cell dissociation
2Measurement precision
If cell aggregates are dissociated into single cells for measurement, then measurement accuracy improves, but process complexity and time requirements increase
Solution Approach 1:
The patent extracts only the necessary measurement information (light scattering properties) directly from the intact cell aggregate suspension, eliminating the need to extract or dissociate individual cells. The measurement is performed on the suspension as-is, removing the complex dissociation step while maintaining the ability to determine cell density parameters
Solution Approach 2:
The measurement system is designed to work with the natural state of cell aggregates in suspension without requiring external intervention to dissociate them. The optical probe measures the suspension properties directly, allowing the cell aggregate system to serve its own measurement needs without additional processing steps
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
Enables inline monitoring and assessment of cell density in cell aggregates, allowing for the control of culture parameters and key process steps without the need for cell dissociation, facilitating GMP-controlled production of cells in large scales.
Implementation Method 1
measuring the permittivity of the cell suspension
Data Source
AI summary
The present disclosure relates to a method of measuring cell density in a cell suspension comprising cell aggregates, the method comprising (i) Measuring the permittivity of the cell suspension; (ii) Comparing the measured permittivity with a predetermined value that is indicative of the cell density, thereby determining the cell density. Further described is a of a permittivity probe for determining the cell density of a suspension cell culture comprising cell aggregates.