Advances in potentiometric chemical sensing systems for clinical and biochemical monitoring applications.

Part I of this dissertation describes the development and analytical performance of a novel potentiometric combination ion/pCO$\\sb2$ sensor design for in vitro and in vivo measurements. An ionophore is incorporated within the gas permeable membranes of conventional and new catheter-type pCO$\\sb2$ sensors. Simultaneous measurements of potentials across the ion-selective/gas permeable membrane and the inner pH sensitive membrane enable continuous monitoring of ionic and pCO$\\sb2$ levels with the same device. A macro-sized K$\\sp{+}$/pCO$\\sb2$ sensor is constructed from a commercial CO$\\sb2$ sensor, and is used to demonstrate the principles and capabilities of the proposed design. A flexible, miniaturized (outer diameter = 1.2 mm) combination K$\\sp{+}$/pCO$\\sb2$ catheter sensor is also described. Continuous (6-h) blood measurements of K$\\sp{+}$ and pCO$\\sb2$ using the macro and catheter-type combination sensors correlate well with conventional bench-top analyzers. Continuous (4-h) intravascular measurements with the combination catheter sensor in dogs also correlate with commercial blood analyzers (R = 0.984 and 0.962 for pCO$\\sb2$ and K$\\sp{+}$). Part II describes novel on-line gas predialysis units that eliminate interferent gases in automated enzyme-based analyzers. An on-line NH$\\sb3$ predialysis coil preceding an immobilized creatinine iminohydrolase (E.C. 3.5.4.21) enzyme reactor enables automated determinations of creatinine in physiological samples. The enzyme converts creatinine to NH$\\sb3$, which is detected by a flow-through potentiometric NH$\\sb3$ detector. The predialyzer removes $>$99.8% of endogenous NH$\\sb3$ (up to 1 mmol/L) from serum and urine samples, ensuring that detector peak potentials are proportional to the logarithm of creatinine concentrations. Serum creatinine determinations (n = 30) using this new method correlate well with an existing colorimetric method (r = 0.996). Removal of interfering CO$\\sb2$ in automated systems employing decarboxylating enzyme coils and potentiometric CO$\\sb2$ detection was also pursued. A new CO$\\sb2$ predialyzer removes $>$99.7% of endogenous CO$\\sb2$ (up to 50 mmol/L) from bioreactor media and serum samples. Measurements of glutamate in bioreactor media using the new CO$\\sb2$ predialyzer, an immobilized glutamate decarboxylase (E.C. 4.1.1.15) reactor coil (which converts glutamate to CO$\\sb2$) and a flow-through CO$\\sb2$ detector demonstrated the effectiveness of the predialyzer in reducing interfering CO$\\sb2$ in such systems.PhDAnalytical chemistryUniversity of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/162425/1/9013879.pd