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The authors developed a laser-diode system that can be used for on-line optical concentration measurements in physiologic systems. Previous optical systems applied to whole blood have been hampered by artifacts introduced by red blood cells (RBCs). The system introduced here uses a commercially available filter cartridge to separate RBCs from plasma before plasma concentration measurements are made at a single wavelength. The filtering characteristics of the Cellco filter cartridge (#4007-10, German-town, MD) were adequate for use in the on-line measurement system. The response time of the filter cartridge was less than 40 seconds, and the sieving characteristics of the filter for macromolecules were excellent, with filtrate-to-plasma albumin ratios of 0.98 +/- 0.11 for studies in sheep and 0.94 +/- 0.15 for studies in dogs. The 635-nm laser diode system developed was shown to be more sensitive than the spectrophotometer used in previous studies (Klaesner et al., Annals of Biomedical Engineering, 1994; 22, 660-73). The new system was used to measure the product of filtration coefficient (Kfc) and reflection coefficient for albumin (delta f) in an isolated canine lung preparation. The delta fKfc values [mL/(cmH2O.min.100 g dry lung weight)] measured with the laser diode system (0.33 +/- 0.22) compared favorably with the delta fKfc obtained using a spectrophotometer (0.27 +/- 0.20) and with the Kfc obtained using the blood-corrected gravimetric method (0.32 +/- 0.23). Thus, this new optical system was shown to accurately measure plasma concentration changes in whole blood for physiologic levels of Kfc. The same system can be used with different optical tracers and different source wavelengths to make optical plasma concentration measurements for other physiologic applications.