Novel instrumentation for real-time monitoring using miniaturized flow systems with integrated biosensors.

A prototype miniaturized Total Chemical Analysis System (muTAS) has been developed and applied to on-line monitoring of glucose and lactate in the core blood of anaesthetized dogs. The system consists of a highly efficient microdialysis sampling interface sited in a small-scale extracorporeal shunt circuit ('MiniShunt'), a silicon machined microflow manifold and integrated biosensor array for glucose and lactate detection with associated computer software for analytical process control. During in-vivo testing the device allowed real-time on-screen monitoring of glucose and lactate with system response times of less than 5 min, made possible by the small dead volume of the microflow system. On-line glucose and lactate measurements were made in the basal state as well as during intravenous infusion of glucose or lactate. The prototype muTAS is currently suitable for trend monitoring but refinements are necessary before application of the system for determination of individual lactate values.

In vitro optimisation of a microdialysis system with potential for on-line monitoring of lactate and glucose in biological samples.

The optimisation and evaluation of the microdialysis component of a prototype miniaturised total analysis system for application in the continuous monitoring of lactate and glucose is reported. The complete unit comprises a high efficiency microdialysis sampling system, a miniaturised microflow manifold with an integrated biosensor array, together with the hardware and software necessary for controlling the flow parameters and monitoring the sensor signals. Sampling occurs via a microdialysis shunt probe which is perfused continuously with a physiological buffered saline solution. The continuous dialysate outflow is presented to the biosensor array, resulting in the appropriate amperometric signals. Aspects of technological significance addressed here include probe membrane size, perfusate flow rate, sample flow rate, temperature change, probe sterilisation procedures, and heparin content of the physiological saline solution employed.

An intravascular microdialysis sampling system suitable for application in continuous biochemical monitoring of glucose and lactate.

Direct sensor implantation for continuous biochemical monitoring has proved disappointing, but microdialysis sampling devices can serve as a biocompatible patient-sensor interface. We propose a novel "MiniShunt" extracorporeal microdialysis sampling circuit designed to sample core blood, and report the performance of different microdialysis probe membrane types and sizes with pumped and non-pumped blood flow in anaesthetised dogs. Discrete microdialysate and plasma samples collected during glucose and lactate monitoring were analysed with a YSI analyzer and showed microdialysis efficiency (% relative recovery) in excess of 95% for both analytes using fibres of greater than 70 mm2 internal surface area. Pumped veno-venous extracorporeal blood microdialysis sampling of this type could provide a suitable interface for future multi-analyte on-line biosensor applications in critically ill patients.