pies, a premeasured flush solution is used to perform a one-point calibration of all the sensors. Two-point calibrations using a second premeasured solution are performed hourly, and test values can be updated every 4-6 min. Although this cannot be considered a continuous or real-time measurement system, this finite lag time in obtaining accurate values for the key critical care analytes is not much longer than the true response times of the optical sensors employed in the continuous in-line measurement systems (2-5 min). The potential clinical use of in-line and on-line bedside testing is limited by the critical issue of biocompatibility. Systems designed for performing measurements in extracorporeal loops, either by direct insertion into the loop or as on-line sampling devices, can be used because patients undergoing cardiac surgery are systemically heparinized (administered large doses of the anticoagulant heparin) during the procedure. This helps to prevent formation of life-threatening emboli in the external loop that can pass back into the patient. More widespread use of extracorporeal in-line chemical sensing systems for other clinical procedures or at the
bedside of intensive care patients is unlikely because the potential benefits of bedside testing may not outweigh the risks associated with implementing an extracorporeal blood loop (e.g., decrease in blood platelet count, increase in complications from bleeding). Implementation of semicontinuous online blood analyzers for routine bedside testing requires the development of a biocompatible in-dwelling catheter sample probe that will enable the automatic sampling of undiluted whole blood directly from the patient, with subsequent downstream measurement of blood gases as well as other critical care analytes via sensors that can be recalibrated periodically for greater accuracy. Continuous in vivo sensors. Although considerable research effort and funds have been expended to date, relatively few catheter-type sensors are currently available for continuous in vivo (intravascular) measurements of critical care analytes. Advances in this technology have been severely limited by the inability to develop small (i.e., 20-gauge or 0.5-mm o.d.), durable, and biocompatible sensors that maintain adequate long-term stability when implanted in vivo. Useful lifetimes of such
sensors ideally should be equivalent to the maximum recommended arterial implant time (72-96 h). To attain such lifetimes, in vivo sensors must retain calibration stability for longer time periods than most conventional macrosize sensors used in laboratory instruments or even some of the newer bedside testing systems. There is no simple and convenient means to fully calibrate (two-point calibration) the sensors once implanted. In some instances, sensor stability is directly related to the design used to miniaturize the sensing technology. For example, when first developed, ion-selective field effect transistors (ISFETs) were touted as an attractive approach to the design of in vivo electrolyte sensors because they used the same polymeric membrane-based ionsensing chemistries employed in macro-laboratory-type instruments (19). Modern microelectronic fabrication techniques allow multiple sensors to be placed on a single implantable transistor chip. However, problems of encapsulation and unstable membrane/gate interfacial potentials have thus far prevented such devices from achieving the level of signal stability required for reliable in vivo measurements.
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ANALYTICAL CHEMISTRY, VOL. 62, NO. 7, APRIL 1, 1990 · 435 A