DESIGN AND DEVELOPMENT OF A MINIATURIZED TOTAL CHEMICAL-ANALYSIS SYSTEM FOR ONLINE LACTATE AND GLUCOSE MONITORING IN BIOLOGICAL SAMPLES

A miniaturised Total chemical Analysis System (mu TAS) for glucose and lactate measurement in biological samples constructed based on an int egrated microdialysis sampling and detection system. The complete syst em incorporates a microdialysis probe for intravascular monitoring in an ex vivo mini-shunt arrangement, and a silicon micromachined stack w ith incorporated miniaturised flow cell/sensor array. The prototype de vice has been developed based on state-of-the-art membrane and printed circuit board technology. The flow-through detection system is based on a three-dimensional flow circuit incorporating silicon chips with s tacked micromachined channels. An integrated biosensor array (comprisi ng enzyme sensors specific for glucose and lactate) is placed at the b ase of the stack allowing the detector to be incorporated within the m u TAS assembly. These glucose and lactate biosensors are prepared usin g photolithographic techniques, with measurement based on the detectio n of hydrogen peroxide at glucose oxidase and lactate oxidase modified platinum electrodes. The resulting amperometric current (at 500 mV vs . Ag/AgCl) is proportional to the concentration of analyte in the samp le. All instrumentation is under computer control and the complete uni t allows continuous on-line monitoring of glucose and lactate, with fa st stable signals over the relevant physiological range for both analy tes. The microdialysis system provides 100% sampling efficiency. Senso r performance studies undertaken include optimisation of sensitivity, linearity, operational stability, background current, storage stabilit y and hydration time. The total system (sampling and detection) respon se time is of the order of 4 min, with sensor sensitivity 1-5 nA mM(-1 ) for glucose and lactate over the range 0.1-35 and 0.05-15 mM, respec tively.