Optical Bioreactor Sensing for Non-Invasive Cell Monitoring
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Solution Overview
Problem
Existing bioreactor systems require physically invasive procedures to determine cell biomass production, leading to contamination risks, product loss, and limited sampling frequency, which are particularly risky for autologous cell therapies.
Innovation Solution
A computer-implemented method and system that use sensor-based data from multiple physical attributes to predict viable cell density and inform process decisions, such as adjusting feed rates and harvest timing, without the need for sample withdrawal.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If physically invasive sampling procedures are used to determine cell biomass production, then measurement precision is improved, but contamination risk and product loss increase
Solution Approach 1:
The patent replaces the mechanical sampling system with an optical sensing system. Sensors mounted on the bioreactor wall use light-based techniques (such as optical coherence tomography or light scattering) to measure cell biomass production non-invasively through the reactor wall, eliminating the need for physical sample withdrawal and associated contamination risks
Solution Approach 2:
The patent introduces an intermediary optical sensing system that mediates between the bioreactor environment and the measurement system. The sensors act as intermediaries by detecting cell biomass production parameters (such as light scattering properties or optical coherence signals) through the bioreactor wall without direct contact with the cell culture, thus preventing contamination while maintaining measurement capability
2Measurement precision
If physically invasive sampling procedures are used to determine cell biomass production, then measurement precision is improved, but product loss increases
Solution Approach 1:
The patent replaces the mechanical sampling system with an optical sensing system that measures cell biomass production through the bioreactor wall without removing cells from the system, thereby eliminating product loss while maintaining measurement precision
Solution Approach 2:
The patent creates an optical copy or representation of the cell biomass production state by measuring optical properties (light scattering, optical coherence) of the cell population through the reactor wall. This optical copy provides measurement information without requiring physical removal of actual cells, thus preventing product loss
3Loss of information
If frequent sampling is performed to monitor cell biomass production, then information accuracy is improved, but time cost and operational complexity increase
Solution Approach 1:
The patent implements continuous monitoring by mounting sensors on the bioreactor wall that can continuously or frequently measure cell biomass production parameters without interruption. This allows real-time tracking of cell culture state information, eliminating the discrete sampling intervals and associated time delays of traditional methods
Solution Approach 2:
The patent replaces the manual sampling and laboratory analysis system with an automated optical sensing system that continuously measures cell biomass production in-situ, eliminating the time required for physical sample withdrawal, transport, and off-line analysis
4Measurement precision
If physically invasive sampling procedures are used to determine cell biomass production, then measurement precision is improved, but device complexity increases
Solution Approach 1:
The patent replaces the complex mechanical sampling system (including sample withdrawal mechanisms, sterile connectors, and off-line analysis equipment) with a simpler optical sensing system mounted on the bioreactor wall that performs measurements non-invasively, thereby reducing overall system complexity while maintaining measurement precision
Solution Approach 2:
The patent creates a universal sensing platform that can be mounted on various bioreactor types and used for different cell culture applications. The optical sensing system serves multiple functions including cell biomass production measurement, cell density monitoring, and process optimization, replacing multiple specialized sampling and analysis devices
Data Source
AI summary
In an aspect, there is provided a computer-implemented method for approximating product production in a bioreactor. The method comprises: providing a bioreactor containing live cells in a substrate, the bioreactor for cultivating, over a time period, a product derived from or of the cells during a manufacturing process; providing two or more sensors for measuring respective two or more different physical attributes of the substrate during the time period; receiving, at a processor, sensor data from the two or more sensors; and determining via the processor, based on a predetermined or recursive algorithm that correlates the sensor data and the product production by independent consideration of the sensor data of the two or more different physical attributes or by multivariate consideration of the sensor data of the two or more different physical attributes, an approximate amount of the product.