A Bluetooth Low-Energy Wireless Sensor Platform for Continuous Monitoring of a Bioreactor Environment during Cell Manufacturing

A wireless sensor platform based on Bluetooth Low-Energy (BLE) technology was designed and prototyped for continuous monitoring of physical conditions and chemical analytes, which could be applied to bioreactors during the cell manufacturing process. Controlling environmental conditions such as pH, oxygen, glucose, temperature, and pressure is vital to ensure the consistency of the manufactured cells and maintain the potency of the product. Current methods to control bioreactor conditions focus only on monitoring the cell culture environment during cell growth, but there is a lack of direct quantification of cell properties to provide an integrated feedback system that can also maintain cell quality. Furthermore, current methods are typically expensive and inflexible for new bioreactor designs. The ultimate goal of this project is to develop a low-cost wireless sensor platform that can incorporate different types of sensors for monitoring both growth conditions and cell quality in various types of bioreactors. This thesis represents the first phase of the project with the development of the sensor platform and prototyping a pH and temperature sensor module along with the platform. Bench tests demonstrated the efficacy of these sensors in continuous monitoring of pH and temperature over several days. With the sensor functionality proven, the next step is to examine the biocompatibility of the sensor, as well as expand the parameters to include oxygen, glucose, and pressure. New sensors, such as those based on the impedimetric technique, will also be developed to direct cell quality evaluation

BPOD: A WIRELESS INTEGRATED SENSOR PLATFORM FOR CONTINUOUS LOCALIZED BIOPROCESS MONITORING

Process parameter spatial inhomogeneities inside cell culture bioreactors has attracted considerable attention, however, few technologies allow investigation of the impact of these variations on process yield. Commercially available sensing probes sit at fixed locations, failing to capture the spatial distribution of process metrics. The bio-Processing online device (bPod) addresses this problem by performing real-time in situ monitoring of dissolved oxygen (DO) within bioreactor cell cultures. The bPod is an integrated system comprised of a potentiostat analog-front-end, a Bluetooth Low Energy microcontroller, and a Clark-type electrochemical DO sensor. The Clark-type sensor uses chronoamperometry to determine the DO percent saturation within a range relevant for mammalian cell culture. The free-floating capsule is packaged inside a 3D-printed biocompatible shell and wirelessly transmits data to a smartphone while submerged in the reactor. Furthermore, the bPod demonstrated a sensitivity of 37.5 nA/DO%, and can be adapted to multiple sensor types, enabling numerous bioprocess monitoring applications