Cost-Effective Sensor for Flow Monitoring in Biologic Microreactors

Continuous nutrient supply of cell cultures in perfused bioreactors requires reliable flow monitoring. This work presents an approach for the flow rate measurement based on low temperature ceramic technology, which allows the direct integration of temperature sensors in the center of fluid channels. Thick film thermistors detect the flow rate in two different operation modes: the calorimetric addresses flow rates from $20~\mu \text{l}$ /min to $80~\mu \text{l}$ /min and the time of flight flow such as up to 1.5 ml/min. The design takes advantage of highly sensitive thermistors with negative temperature coefficient, and optimized heat exchange due to the direct thermal contact between fluid and temperature probe. In addition to calorimetric evaluation, the temperature course as a function of time is used to detect the time of flight. This allows the tracking of the flow rate independent from the thermistor's temperature characteristic using the temperature maximum as marker. Cross-correlation applied to this temperature problem significantly improves the detection accuracy for the time of flight. Based on temperature and flow measurement data, it was proven that a fit function could replicate the flow rate as a function of the difference in time of flight between two thermistor positions with a deviation less than 4 %. The evaluation of time of flight data can extend the operation range of the sensor by two orders of magnitude. Applying this signal processing, the same method can be applied even for low flow rates, with a measurement range from $30~\mu \text{l}$ /min to $1500~\mu \text{l}$ /min.