Real-Time pH Control in Parallel Culture Wells
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Solution Overview
Problem
Conventional workflows in bioprocess control systems require sequential measurement and adjustment of pH in culture wells, leading to inaccuracies due to pH fluctuations during the measurement cycle, which can impact cell growth, especially for cells requiring a narrow pH range.
Innovation Solution
A system that initiates pH control in parallel culture wells by comparing measured pH values to predetermined values in real-time, allowing for immediate adjustments using a pH adjustment system, with measurements and controls performed concurrently across multiple wells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If sequential measurement and adjustment of pH is performed in culture wells, then measurement accuracy is improved, but time consumption increases and pH fluctuations occur during the measurement cycle
Solution Approach 1:
The system divides the microplate into multiple individual culture wells that can be measured and controlled independently in parallel. Each well's pH is measured and adjusted separately through dedicated fluidic channels and valves, allowing simultaneous processing of multiple wells without sequential delays.
Solution Approach 2:
The system combines multiple measurement and adjustment operations into a single integrated cycle. pH measurement, deviation detection, and adjustment actions are merged and executed concurrently across multiple wells, eliminating the time loss associated with sequential processing while maintaining measurement accuracy through the integrated control architecture.
2Reliability
If sequential pH control is performed for each culture well, then control accuracy is improved, but productivity decreases
Solution Approach 1:
The system segments the control operations into independent parallel streams for each culture well. Each well has its own measurement and adjustment pathway controlled by individual valves and fluidic channels, enabling multiple wells to be processed simultaneously while maintaining the same control accuracy as sequential methods.
Solution Approach 2:
The system maintains continuous pH control across all culture wells by performing measurements and adjustments concurrently rather than intermittently. The parallel architecture allows the useful action of pH control to continue simultaneously in multiple wells, increasing throughput while preserving control accuracy through continuous monitoring and adjustment.
3Loss of information
If pH measurement cycle is extended to cover all culture wells, then complete monitoring is improved, but pH fluctuations increase affecting cell growth
Solution Approach 1:
The system segments the monitoring process into parallel independent measurements for each culture well. This allows complete monitoring of all wells to be achieved simultaneously rather than sequentially, reducing the total measurement cycle time and minimizing pH fluctuations that would occur during extended sequential monitoring periods.
Solution Approach 2:
The system implements continuous pH monitoring across all culture wells through parallel measurement and adjustment operations. By maintaining continuous control rather than allowing gaps between sequential measurements, the system ensures complete monitoring coverage while preventing harmful pH fluctuations that would affect cell growth during extended measurement cycles.
Data Source
AI summary
A workflow and associated system for controlling pH is described that allows for real-time pH adjustment in parallel culture wells of a microplate. For example, a biological process control system comprised of a pH measurement system, a controller, and a pH adjustment system implements a closed control loop, where a pH of a culture well measured by the pH measurement system is compared to a predetermined pH for the culture well, and, if there is a deviation, a pH adjustment system adjusts the pH in the culture well to correct the deviation as the system continues on to measure, evaluate, and adjust, if needed, remaining microplate culture wells. Therefore, by performing per-well pH evaluation and adjustment in real-time upon receiving the measured pH rather than waiting until pH of all culture wells are measured, the measured pH used as a basis for pH adjustment is a current, accurate measurement.