The pain and risk of infection associated with invasive blood sampling for blood gas measurements necessitate the search for reliable noninvasive techniques. In this work we developed a novel rate-based noninvasive method for a safe and fast assessment of respiratory status. A small sampler was built to collect the gases diffusing out of the skin. It was connected to a CO2 sensor through gas-impermeable tubing. During a measurement, the CO2 initially present in the sampler was first removed by purging it with nitrogen. The gases in the system were then recirculated between the sampler and the CO2 sensor, and the CO2 diffusion rate into the sampler was measured. Because the measurement is based on the initial transcutaneous diffusion rate, reaching mass transfer equilibrium and heating the skin is no longer required, thus, making it much faster and safer than traditional method. A series of designed experiments were performed to analyze the effect of the measurement parameters such as sampler size, measurement location, subject positions, and movement. After the factor analysis tests, the prototype was sent to a level IV NICU for clinical trial. The results show that the measured initial rate of increase in CO2 partial pressure is linearly correlated with the corresponding arterial blood gas measurements. The new approach can be used as a trending tool, making frequent blood sampling unnecessary for respiratory status monitoring.

The continuous monitoring of transcutaneous gases is an integral part of neonatal intensive care. Present monitors measure the equilibrating values of these gases by raising the skin temperature to 42°C or above. Because neonatal skin is very sensitive and delicate, this often leads to serious skin injuries. In this work, we present a new approach to the noninvasive measurement of transcutaneous partial pressure of carbon dioxide (tcpCO2) based on the initial pseudo steady state diffusion rates instead of the mass-transfer equilibrium. Because we are following initial diffusion rates, each measurement takes no more than a few minutes. Additionally, raising the surface temperature is not required, thus, skin irritation and burns are highly unlikely. A dual-chamber diffusion vessel with either porcine skin or dialysis membrane placed between the two chambers was used to mimic neonatal skin. LI-820 CO2 Analyzer was used to measure the CO2 diffusing through the membrane or skin. Initial experiments on adult human skin under varying physical activities, food intake and breathing patterns showed a strong influence of the various conditions on the amount of CO2 diffusing through skin. These initial findings suggest that this method can be used not only on neonates but to a wider population of patients.

Although online monitoring of dissolved oxygen (DO) and carbon dioxide (DCO2 ) is highly desirable in bioprocesses, small-scale bioreactors are usually not monitored due to the lack of suitable sensors. Traditional electrochemical sensors are usually not used because they are bulky and invasive. Disposable optical sensors are small and only partially invasive, but there are concerns regarding the toxicity of the patch and the phototoxicity of the illuminating light. Here we present a novel, noninvasive, rate-based technique for monitoring DO and DCO2 in cell cultures. A silicone sampling loop which allowed the diffusion of O2 and CO2 through its wall was inserted inside a bioreactor, and then flushed with N2 until the CO2 and O2 inside the loop were completely removed. The gas inside the loop was then allowed to recirculate through gas impermeable tubing to the O2 and CO2 sensors. We have shown that by measuring the initial diffusion rate we were able to determine the partial pressures of the two gases in the culture. The technique could be readily automated and measurements could be made in minutes. It was tested in demonstration experiments by growing murine hybridoma cells in a T-flask and a spinner-flask at 37°C. The results were comparable to those measured with commercially available fluorescence-based patch sensors. These results show that the rate-based method is an effective way to monitor small-scale cell cultures. This measurement mechanism can be easily built into disposable cell culture vessels for facile use.

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