Optical Interface for Disposable Bioreactor Monitoring
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Solution Overview
Problem
Disposable bioreactors made of flexible, biocompatible polymers face challenges in continuous and reliable online monitoring of pH and dissolved oxygen due to size constraints, electrical grounding issues, and maintaining sterility, which are not easily addressed by traditional electrochemical probes.
Innovation Solution
The use of fluorescent optical sensor materials and optical interfaces that allow for the selection and installation of appropriate fluorophores and optical designs at the bioreactor site, utilizing fiber optic or etendue-conserving optics to maximize signal collection and minimize photo-degradation, while maintaining sterility and optimizing the optical transmission properties of the bioreactor materials.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Difficulty of detecting and measuring
If electrochemical probes are used for monitoring in disposable bioreactors, then measurement capability is provided, but reliability deteriorates due to grounding issues and electrical ingress noise in polymeric bioreactors
Solution Approach 1:
The patent replaces electrochemical probes with optical sensors that use light instead of electrical signals. This substitution eliminates grounding issues and electrical noise problems inherent in polymeric disposable bioreactors, while maintaining the ability to monitor pH and dissolved oxygen levels reliably
Solution Approach 2:
The patent introduces optical fibers as an intermediary medium to transmit measurement signals. The optical fibers deliver excitation light to fluorophores and collect emitted light signals, serving as a non-conductive bridge that avoids electrical grounding issues while enabling continuous monitoring in disposable bioreactor systems
2Difficulty of detecting and measuring
If electrochemical probes are inserted into disposable bioreactors, then monitoring function is achieved, but sterility is compromised due to difficulty in maintaining sterile system
Solution Approach 1:
The patent applies preliminary sterilization to the entire disposable bioreactor system including integrated optical sensors before use. The bioreactor is pre-sterilized through gamma or beta radiation, and the optical sensors are sterilized alongside the bioreactor components, eliminating the need to maintain sterility during probe insertion and operation
Solution Approach 2:
The patent employs disposable optical sensors that are discarded after single use. These sensors are pre-sterilized and integrated into disposable bioreactor systems, eliminating the need for complex sterilization maintenance during operation since the entire system is replaced after one use
3Difficulty of detecting and measuring
If rigid glass and steel probes are mounted on polymeric bioreactor surfaces, then measurement is enabled, but ease of operation deteriorates due to difficulty in mounting and sealing
Solution Approach 1:
The patent uses flexible optical sensors and thin-film fluorophore coatings that can conform to the flexible polymeric bioreactor surfaces. These flexible optical components can be easily mounted on or integrated into the disposable bioreactor without requiring rigid mounting structures or complex sealing mechanisms
Solution Approach 2:
The patent merges the optical sensing components directly with the bioreactor structure during manufacturing. The fluorophores are incorporated into the bioreactor walls or mixed with the bioreactor materials, creating an integrated system that eliminates separate mounting and sealing operations
4Reliability
If fluorescent optical sensor materials are used, then reliability of monitoring is improved, but loss of substance increases due to photo-degradation of fluorophores
Solution Approach 1:
The patent employs periodic or pulsed excitation of fluorophores rather than continuous illumination. By using intermittent light pulses to excite the fluorophores, the system reduces cumulative photo-degradation while maintaining sufficient signal generation for reliable monitoring over the disposable bioreactor's operational lifetime
Solution Approach 2:
The patent uses excess fluorophore material deposited on the bioreactor surfaces. By providing a higher concentration of fluorophores than the minimum required for detection, the system compensates for photo-degradation losses over time, ensuring sufficient signal strength throughout the operational period
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
This approach enables reliable, low-drift, and sterile monitoring of analytes like oxygen, pH, and glucose, reducing photo-degradation and improving signal-to-noise ratio, thus addressing the limitations of traditional probes in disposable bioreactors.
Implementation Method 1
The use of fluorescent optical sensor materials and optical interfaces that allow for the selection and installation of appropriate fluorophores and optical designs
Implementation Method 2
utilizing fiber optic or etendue-conserving optics to maximize signal collection
Data Source
AI summary
A port assembly for use with a polymeric bioreactor bag includes the following components:i) a hollow port member made from a material which can be fusibly affixed to the wall surface of the bioreactor bag;ii) at least one fluorophore spot positioned on the port member;iii) a conduit for conveying excitation light from an optical source to the fluorophore, which conduit can be a lens, a curved parabolic collimator, a shaped reflector or a wave guide; andiv) a second conduit for conveying fluorescent emission light from the excited fluorophore to a photo-detector, which second conduit although different from the first, can likewise be a lens, a curved parabolic collimator, a shaped reflector or a wave guide.