A lightweight measuring device for the continuous in vivo monitoring of glucose by means of ultraslow microdialysis in combination with a miniaturised flow-through biosensor

Background: Tight regulation of blood glucose levels from patients suffering from diabetes mellitus can significantly reduce the complications associated with this disease. For this reason, elaborate research efforts have been devoted to the development of a glucose sensor for the continuous in vivo monitoring of glucose. Although the use of microdialysis as a sampling interface between the body and the biosensor is widely accepted, a major drawback of conventional microdialysis is the limited in vivo recovery. Here, ultraslow microdialysis is proposed in order to obtain (near) quantitative in vivo recoveries. To avoid, however, unacceptable long delay times, the need for a small and low dead volume measuring device was recognised. Methods: A portable lightweight measuring device for continuous in vivo monitoring of glucose in subcutaneous tissue is presented. The measuring device consists of a miniaturised flow-through biosensor, connected to a microdialysis probe and a semi-vacuum pump. The biosensor is based on the amperometric detection of hydrogen peroxide after conversion of glucose by immobilised glucose oxidase. A portable potentiostat equipped with data logging is used for detection and registration. Results: The device was validated for its accuracy, precision, linearity, sensitivity, selectivity and stability during ex vivo and in vivo experiments. The linearity was found to be up to 30 mmol/l with a limit of detection of 0.05 mmol/l. The precision, depending on the biosensor tested was found to be 2-4%. No contribution to the signal could be observed from several tested electroactive species. The accuracy was found to be well in accordance with the criteria set for methods of Self Monitoring of Blood Glucose for patients with diabetes mellitus. The biosensors could be used for up to 3 days in the continuous mode. In vivo monitoring of glucose in dialysate of subcutaneous sampled tissue during glucose tolerance tests in healthy volunteers demonstrated the potential of this measuring device. Conclusions: A portable lightweight measuring device is presented which can measure continuously glucose in vivo without excessive calibration steps. The performance characteristics determined justify the application of this measuring device for the in vivo monitoring of glucose in subcutaneous sampled interstitium of diabetic patients. (C) 2002 Elsevier Science B.V. All rights reserved.