Fabry-Perot Etalon Sensing for Cell Viability and Protein Aggregation
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Solution Overview
Problem
Existing techniques for measuring cell densities and protein aggregates are often destructive, time-consuming, expensive, and lack real-time, non-destructive monitoring capabilities, particularly in bioprocesses like monoclonal antibody production, leading to reduced data accuracy and process optimization.
Innovation Solution
The use of a Fabry Perot etalon in a photodetector window without an antireflective coating, combined with near-infrared spectroscopy, allows for non-destructive, real-time monitoring of cell viability and protein aggregation by detecting changes in refractive index and absorption, enabling in situ measurements during bioprocessing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If destructive measurement techniques are used to measure cell density and protein aggregates, then measurement accuracy can be achieved, but the cells are killed and real-time monitoring is lost
Solution Approach 1:
The patent replaces destructive mechanical sampling and staining techniques with non-invasive optical measurement using Fabry-Perot interferometry. The system uses light waves to detect refractive index changes in cells and protein aggregates without physical contact or sample removal, enabling real-time monitoring while preserving cell viability.
Solution Approach 2:
The patent measures changes in refractive index as a parameter to detect cell viability and protein aggregation. By monitoring the shift in refractive index caused by light interference patterns, the system can detect physiological changes in cells and aggregate formation without destroying the samples, thus maintaining real-time monitoring capability.
2Measurement precision
If offline sample analysis is performed, then comprehensive analysis can be conducted, but time consumption increases and real-time process control is lost
Solution Approach 1:
The patent enables continuous real-time measurement of cell density and protein aggregates during the bioprocess. The Fabry-Perot interferometer provides uninterrupted optical monitoring without requiring sample withdrawal, allowing the process to continue without interruption while maintaining comprehensive analysis capability through continuous data collection.
Solution Approach 2:
The system performs self-contained optical measurement directly in the bioreactor without requiring external laboratory equipment or manual sampling. The interferometer uses the existing light source and detector system to automatically detect and quantify cells and aggregates, eliminating the need for time-consuming offline analysis procedures.
3Measurement precision
If expensive equipment and consumables are used for cell analysis, then measurement accuracy is improved, but operational cost increases
Solution Approach 1:
The patent employs a multi-functional optical system that can measure multiple parameters (cell density, viability, protein aggregate concentration) using a single Fabry-Perot interferometer setup. This universal approach eliminates the need for multiple specialized expensive instruments and consumables, reducing operational costs while maintaining comprehensive measurement accuracy.
Solution Approach 2:
The system replaces expensive mechanical sampling, staining, and microscopy equipment with a cost-effective optical interferometry system. By using light-based detection instead of physical sampling and chemical staining, the patent significantly reduces the need for expensive consumables and equipment maintenance while achieving comparable or superior measurement accuracy.
4Loss of information
If frequent sampling is performed to obtain more data points, then process monitoring improves, but cell exposure to external conditions increases and data accuracy decreases
Solution Approach 1:
The patent provides continuous real-time monitoring that eliminates the need for discrete frequent sampling. The interferometer continuously measures optical properties of the cell culture, providing an uninterrupted data stream that maintains high data density while avoiding the errors introduced by repeated sampling and external exposure.
Solution Approach 2:
The system performs in-situ measurement directly in the bioreactor without requiring sample withdrawal. This self-contained approach allows unlimited data points to be collected without increasing cell exposure to external conditions, as the measurement occurs within the closed bioreactor environment using non-invasive optical detection.
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 provides rapid, accurate, and continuous monitoring of cell viability and protein aggregation, reducing sample withdrawal needs and minimizing external exposure of cells, thereby enhancing process control and product quality.
Implementation Method 1
Fabry perot interferometry for measuring cell viability
Implementation Method 2
detecting changes in refractive index and absorption
Implementation Method 3
near-infrared spectroscopy, allows for non-destructive, real-time monitoring
Implementation Method 4
detecting changes in refractive index and absorption
Data Source
AI summary
A method for studying cell viability and protein aggregation involves establishing a Fabry Perot etalon signal within an optical spectroscopic feature, e.g., in the near infrared region. Protein aggregation and cell viability can be reflected by changes observed in the magnitude of the Fourier Transform peaks observed in the frequency or space domain associated with the contrast of the etalon. In short, the presence of viable cells and protein aggregates can degrade the etalon contrast of an etalon window. In some cases, the concentration of cells and monomeric protein can be measured as well.