Carbon dioxide, oxygen, and pH monitoring in complex media using a combination of microdialysis and colorimetry

An approach which combines microdialysis and colorimetry is applied to pCO2, pO2, and pH monitoring in the following applications: an ex vivo implementation, an intravascular catheter, and a cell culture flow loop. The potential of this approach is evaluated in terms of signal to noise ratio, reliability, response time, and long-term stability. An investigation includes the development of the three implementations and evaluations within buffer, cell culture media, and heparinized whole blood. Aspects of the development process include identifying sources of noise inherent with this process (and elimination/minimization where possible); construction of the implementations; selection of indicators appropriate for these applications; residence time studies to determine equilibration time; method of delivering precise flow rates; selection of membrane material; interface geometric design; and, optical cell design.;All three sensors (pH, pCO2, and pO2), operating simultaneously, are tested in buffer, blood, and fetal bovine serum. Long-term studies are performed over seven days in buffer, four days in culture, and fourteen hours in blood. For the ex vivo application, resolutions in buffer are +/-0.003 for pH, +/-1.5 mmHg for pO 2, and +/-0.5 mmHg for pCO2 with response times in blood of 1.8, 2.1, and 4.8 minutes. A comparison of a blood gas analyzer (Chrion 348) with the three sensors exposed to a recirculating flow of blood for 14 hours show R2 values of 0.996, 0.976, and 0.928 for the pCO2, pO2, and pH sensors, respectively. All three sensors demonstrate lower standard deviations when compared with the latest available blood gas, analyzer (Chiron 348) at two buffer concentration levels using a sample size of seven. Results from the catheter implementation demonstrate a +/-0.01 pH unit resolution, a +/-2 mmHg pCO2, resolution with a 7.5 minute and a 15 minute response time, respectively. A four day study in 10% fetal bovine serum shows R2 values (compared to a Radiometer ABL30 Blood Gas Analyzer) of 0.941 for pCO2, 0.877 for pO 2, and 0.541 for pH. During this study, a comparison is made between pH sensor flow rate and the error of the pH sensor. (Error is measured by the difference between the analyzer and the pH sensor values). The comparison shows a relationship between this difference and flow rate suggesting the importance of precisely controlled flow rates.;There were several unexpected findings observed during this research. For example, one finding suggests compliance, observed in the sensor output, may be caused by outgassing of micro-bubbles with flow through micro-bore resistance capillaries. This led to the implementation of an alternative approach to sensor evaluation, consisting of intermittent perfusate flow. Another study during this work shows that increasing membrane fiber length and perfusate flow rate can decrease oxygen sensor rise time. The oxygen sensor also exhibited a hysteresis effect with increasing and subsequent decreasing step changes in oxygen tension. Another finding shows little difference in equilibration time between blood and buffer with the pCO2 and pO2 sensors and a significant effect with the pH sensor.;This work suggests the approach of combining microdialysis with colorimetry applied to pH, pCO2, and pO2 monitoring has the potential for long-term stability in complex media with good response times and high signal to noise ratios.