Date of Degree
PhD (Doctor of Philosophy)
Mark A. Arnold
The long-term complications of diabetes can be dramatically reduced with tight glycemic control. Although the current invasive technology for measuring blood glucose is effective, it not well suited for the real-time measurements necessary for tight control. Near infrared (NIR) absorption spectroscopy, coupling with multivariate calibration modeling, can potentially provide portable, rugged and low-cost instrumentation for continuous glucose sensing. An optical microsensor that can be used in conjunction with an ultrafiltration sampling probe is under development for continuous glucose measurements in interstitial fluid (ISF) collected from subcutaneous tissue.
The first part of this research focused on the development of an algorithm for eliminating of effect of temperature variance on NIR glucose measurements. Spectra of 80 bovine blood ultrafiltrate samples were collected under five different temperatures by using a Fourier transform (FT) NIR spectrometer. Based on the fundamental properties of digital Fourier filtering, baseline variations created by difference in the temperature of the blood ultrafiltrate samples were shown to be eliminated by using an optimized Gaussian shape filter response function. PLS calibration models combined with digital Fourier filtering provided standard errors of prediction in the range of 0.3-0.4 mM for sample with temperatures between 25-40 °C.
Before applying the microsensor to animal or human measurements, a testing platform was designed and constructed for the eventual purpose of evaluating the ability of the microsensor to follow glucose concentration transients. A series of computer-controlled pumps were used in combination with an ultrafiltration probe to create glucose transients and deliver the corresponding samples to the spectrometer for analysis. NIR spectra were collected continuously as the concentrations of glucose, urea, and lactate were varied independently. Glucose transients were followed over periods of days by using either partial least squares (PLS) or net analyte signal (NAS) calibration methods.
The NAS calibration method and a modified Hybrid Linear Analysis (HLA) method were investigated for monitoring the concentrations of glucose and lactate during microbial fermentations. An UF-sampling probe is used to collect samples of the fermentation broth and deliver these samples to the spectrometer for continuous analysis. The established NAS and modified-HLA calibration models provided glucose and lactate concentration measurements with mean percentage errors of 2 and 3%, respectively. These calibration functions were demonstrated capable of accurate concentration measurements several days beyond the formal calibration process.
Lastly, NIR spectra of whole bovine blood samples were used to demonstrate the ability to measure glucose in blood with different levels of hematocrit. Calibration functions were based on PLS modeling and the effective models were developed for measurements from absorbance and single-beam NIR spectra. The method of multiplicative scatter correction was found to be particularly effective in reducing the impact of light scattering caused by the red blood cells at different hematocrit levels. These findings imply that nondestructive NIR spectroscopy has the potential to measure glucose without consuming blood, thereby reducing phlebotomy blood loss in neonates and potentially decreasing the frequency of red blood cell transfusion for this fragile patient population.
Copyright 2013 Jue Qian
Qian, Jue. "Glucose Monitoring in Various Matrices with Near-Infrared Spectrometry and Chemometrics." PhD diss., University of Iowa, 2013.