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Integrated multi-sensor system for parallel in-situ monitoring of cell nutrients, metabolites, cell density and pH in biotechnological processes

 
: Mross, Stefan; Zimmermann, Tom; Winkin, Nadine; Kraft, Michael; Vogt, Holger

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Sensors and Actuators. B 236 (2016), S.937-946
ISSN: 0925-4005
Englisch
Zeitschriftenaufsatz
Fraunhofer IMS ()
bioprocess monitoring; multi-sensor system; In-situ monitoring; enzyme sensors; cell density sensor; pH sensor

Abstract
We report on a multi-sensor system for the parallel in-situ monitoring of cell nutrients, metabolites, cell density and pH in biotechnological processes. The fabrication process of the sensor chip, based on a CMOS process flow, is suitable for integration into standard processes and mass production of the system. The integration of enzyme sensors for wide concentration ranges, an impedance-based sensor and a pH sensor on one silicon chip for in-situ applications in bioreactors, fabricated in a CMOS-based process flow, is demonstrated for the first time to our best knowledge. Measurements of glucose and lactate concentrations in a wide range are shown with linear ranges up to 600 mM and 900 mM, respectively. Cell density is determined via conductivity changes of a cell suspension and measurements are performed up to 15 g/l dry cell weight. The pH sensor is based on C-V measurements at an electrolyte-insulator-semiconductor structure and able to measure pH in a range from pH 3 to pH 12. All sensors are successfully employed in the monitoring of cultures of Saccharomyces cerevisiae or Lactobacillus acidophilus.

: http://publica.fraunhofer.de/dokumente/N-411022.html