Bioprocess Analysis Sensor System for Real-Time Monitoring of 'In-Vitro' Protein Production Variables


Author/Creator ORCID




Computer Science and Electrical Engineering


Engineering, Electrical

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Real-time monitoring of bioprocesses enables one to track changes and correct abnormalities. Multiple arrangements for the apparatus of such bioprocesses has led to the need of universal, portable, versatile, real-time bioprocess monitoring systems. This dissertations presents a new class of opto-electronic transducers that can be used to measure multiple bioprocess variables without the need to switch the optics or hardware. This allows flexibility closer to the lab-grade devices with compact size similar to a dedicated sensor. The versatile instrumentation of the sensor system is capable of seamlessly switching between pH, Dissolved Oxygen (DO), and Green Fluorescent Protein (GFP) measurement modes, and is capable of auto recognition of the sensor type. The pH and DO were measured using optical chemical sensors that were interrogated using the specialized opto-electronic transducer. A software visual interface was developed for control and data logging for the bioprocess analysis sensor system measurements. The principle of ratiometric fluorescence was used for pH measurements, and that of fluorescence-lifetime for DO measurements. Fluorescent emissions as a result of blue excitations were directly measured in the case of GFP. GFP is intended to be used as a biomarker for real-time monitoring of target protein production. A fixed-length extension for the optical fiber electrode (optrode) of the opto-electronic transducer was modeled and implemented to rectify anomalies in signal due to movement of optrode in a GFP bioprocess. GFP measurements were further analyzed by observing rate of change of protein expression/generation. Expression and rate signals were processed in real-time and post-processed using digital filters. The bioprocess analysis sensor system was used to monitor protein purification as well. The instrumentation of the sensor system, when modified by replacing the excitation LEDs and photodiode, was used to measure UV absorbance for quantification of proteins. Quantum dots were used to convert UV light to red light, thus enabling UV absorbance detection with the visible range photodiode already present on the sensor. A comparative study was conducted to evaluate the UV absorbance sensor and quantum dot sensor. The developed system constitutes common instrumentation for measuring either pH, DO, GFP, or UV absorbance. It has been tested in actual bioprocesses and protein production processes to assess the measurement accuracy of each variable, and has been found acceptable for continuous bioprocess monitoring.