Development and Implementation of a Compensation Technique for Luminescent Sensors

Despite offering high specificity and speed compared to other methods, the dependency of the response of an enzymatic sensor on ambient oxygen concentrations. To investigate this issue, a reaction-diffusion model was developed using the finite element method. Due to the growing population of people with diabetes, glucose was chosen as a model analyte. This glucose sensor model was used to examine the oxygen dependency and the resulting inaccuracy of glucose predictions. To improve the accuracy of glucose predictions, an oxygen compensation method was developed which utilizes a variable calibration curve where the fit parameters are dependent on the ambient oxygen concentration. This allows a unique calibration curve to be obtained for every oxygen concentration. Glucose predictions made with this compensation technique were found to be within clinically acceptable regions more than 95% of the time whereas predictions made without compensation were clinically acceptable less than 50% of the time.

In order to apply this compensation technique for real-time analysis, ambient oxygen concentrations must be measured in parallel with the response of the glucose sensor. Despite the growing need for multi-analyte sensors such as this, a suitable method for monitoring multiple responses in vivo has yet to be developed. Due to the measurement flexibility provided by luminescence, a time-domain luminescence lifetime measurement system was developed. The Dynamic Rapid Lifetime Determination (DRLD) approach utilizes a dynamic windowing algorithm to select the optimal window width for calculation of lifetimes using an integrative approach. This method was demonstrated with an oxygen-sensitive luminophore and shown to accurately determine lifetime values six orders of magnitude faster than traditional methods.

This method was then extended to simultaneous measurement of the lifetimes from two luminophores (Dual DRLD or DDRLD) for multi-analyte applications. The ability of DDRLD to calculate lifetimes was demonstrated using temperature and oxygen sensing films. Similar to oxygen compensation of glucose sensors, a temperature compensation method was investigated for oxygen sensors. Lifetimes of the temperature sensing films for dual films measurements made using DDRLD were not significantly different than individual film measurements using DRLD. Oxygen responses for dual films followed the same trend as individual film measurements and displayed a minimal difference on average (2%). Real-time, dynamic temperature and oxygen predictions were demonstrated using DDRLD in conjunction with temperature compensation of the oxygen sensing film response.