[Miniature thin layer biosensors which are sensitive to glutamate and glutamine]

Integrated thin film biosensors for simultaneous measurement of L-glutamine and L-glutamate in a micro-flow cell were developed. Due to a novel glutaminase with an activity optimum in the neutral pH range a direct monitoring of glutamine in mammalian cell culture medium could be performed. The glutamine bienzyme sensor was prepared by coimmobilization of glutaminase with glutamate oxidase within a photo patterned poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogel membrane. The sensor response is linear in the concentration range of 55 mmol to 10 mmol glutamine/l. Additionally a glutamate biosensor is integrated on the sensor chip for difference measurement of possible glutamate interferences. The sensor chip can be used for at least 300 measurements without any alteration in the performance of its sensors. A new sensor chip with an integrated flow cell provides the possibility of simultaneous measurement of four different parameters at a cell volumina of 1 ml. Completing the microsystem a battery operated surface mounted device (SMD) potentiostat was developed to get a "lab on chip".