Gerard L. Coté

Optical glucose sensing in biological fluids: an overview.

Recent technological advancements in the photonics industry have led to a resurgence of interest in optical glucose sensing and to realistic progress toward the development of an optical glucose sensor. Such a sensor has the potential to significantly improve the quality of life for the estimated 16 million diabetics in this country by making routine glucose measurements more convenient. Currently over 100 small companies and universities are working to develop noninvasive or minimally invasive glucose sensing technologies, and optical methods play a large role in these efforts. This article reviews many of the recent advances in optical glucose sensing including optical absorption spectroscopy, polarimetry, Raman spectroscopy, and fluorescent glucose sensing. In addition a review of calibration and data processing methods useful for optical techniques is presented.

Theoretical justification of wavelength selection in PLS calibration : Development of a new algorithm

The mathematical basis of improved calibration through selection of informative variables for partial least-squares calibration has been identified. A theoretical investigation of calibration slopes indicates that including uninformative wavelengths negatively affect calibrations by producing both large relative bias toward zero and small additive bias away from the origin. These theoretical results are found regardless of the noise distribution in the data. Studies are performed to confirm this result using a previously used selection method compared to a new method, which is designed to perform more appropriately when dealing with data having large outlying points by including estimates of spectral residuals. Three different data sets are tested with varying noise distributions. In the first data set, Gaussian and log-normal noise was added to simulated data which included a single peak. Second, near-infrared spectra of glucose in cell culture media taken with an FT-IR spectrometer were analyzed. Finally, dispersive Raman Stokes spectra of glucose dissolved in water were assessed. In every case considered here, improved prediction is produced through selection, but data with different noise characteristics showed varying degrees of improvement depending on the selection method used. The practical results showed that, indeed, including residuals into ranking criteria improves selection for data with noise distributions resulting in large outliers. It was concluded that careful design of a selection algorithm should include consideration of spectral noise distributions in the input data to increase the likelihood of successful and appropriate selection.

Measurement and calculation of the two-dimensional backscattering Mueller matrix of a turbid medium

We present both experimental and Monte Carlo-based simulation results for the diffusely backscattered intensity patterns that arise from illumination of a turbid medium with a polarized laser beam. A numerical method that allows the calculation of all 16 elements of the two-dimensional Muller matrix is used; moreover, it is shown that only seven matrix elements are independent. To validate our method, we compared our simulations with experimental measurements, using a turbid medium consisting of 2.02-microm -diameter polystyrene spheres suspended in deionized water. By varying the incident polarization and the analyzer optics for the experimental measurements, we obtained the diffuse backscattering Mueller matrix elements. The experimental and the numerical results are in good agreement.

Noninvasive optical polarimetric glucose sensing using a true phase measurement technique

The development and testing of a noninvasive true phase optical polarimetry sensing system to monitor in vivo glucose concentrations is described. To demonstrate the applicability of this optical sensor for glucose movement, the authors calibrate the system and then test it in vitro using both a glass test cell filled with glucose solution in the physiologic range, with a path length of 0.9 cm to approximate the 1-cm path length present in the anterior chamber of the eye, and then on an excised human eye. The technique used helium neon laser light which was coupled through a rotating linear polarizer along with two stationary linear polarizers and two detectors to produce reference and signal outputs whose amplitudes varied sinusoidally with a frequency of twice the angular velocity of the rotating polarizer, and whose phase was proportional to the rotation of the linear polarization vector passing through the glucose solution.<<ETX>>

Light backscattering polarization patterns from turbid media: theory and experiment.

We present both experimental measurements and Monte-Carlo-based simulations of the diffusely backscattered intensity patterns that arise from illuminating a turbid medium with a polarized laser beam. It is rigorously shown that, because of axial symmetry of the system, only seven elements of the effective backscattering Mueller matrix are independent. A new numerical method that allows simultaneous calculation of all 16 elements of the two-dimensional Mueller matrix is used. To validate our method we compared calculations to measurements from a turbid medium that consisted of polystyrene spheres of different sizes and concentrations in deionized water. The experimental and numerical results are in excellent agreement.

Lymph Flow, Shear Stress, and Lymphocyte Velocity in Rat Mesenteric Prenodal Lymphatics

Objective: To measure lymphocyte velocity, lymphatic contraction, and shear stress in phasically contracting lymphatics in situ.

Nanofluidic Biosensing for β-Amyloid Detection Using Surface Enhanced Raman Spectroscopy

Trace detection of the conformational transition of beta-amyloid peptide (Abeta) from a predominantly alpha-helical structure to beta-sheet could have a large impact in understanding and diagnosing Alzheimers disease. We demonstrate how a novel nanofluidic biosensor using a controlled, reproducible surface enhanced Raman spectroscopy active site was developed to observe Abeta in different conformational states during the Abeta self-assembly process as well as to distinguish Abeta from confounder proteins commonly found in cerebral spinal fluid.

Development and calibration of an automated Mueller matrix polarization imaging system

The high fatality rate associated with the late detection of skin cancer makes early detection crucial in preventing death. The current method for determining if a skin lesion is suspect to cancer is initially based on the patients and physicians subjective observation of the skin lesion. Physicians use a set of parameters called the ABCD (asymmetry, border, color, diameter) rule to help facilitate diagnosis of potential cancerous lesions. Lesions that are suspicious then require a biopsy, which is a painful, invasive, and a time-consuming procedure. In an attempt to reduce the aforementioned undesirable elements currently associated with skin cancer diagnosis, a novel optical polarization-imaging system is described that has the potential to noninvasively detect cancerous lesions. The described system generates the full 16-element Mueller matrix in less than 70 s. The operation of the system was tested in transmission, specular reflection, and diffuse reflectance modes, using known samples, such as a horizontal linear polarizer, a mirror, and a diffuser plate. In addition, it was also used to image a benign lesion on a human subject. The results of the known samples are in good agreement with their theoretical values with an average accuracy of 97.96% and a standard deviation of 0.0084, using 16 polarization images. The system accuracy was further increased to 99.44% with a standard deviation of 0.005, when 36 images were used to generate the Mueller matrix.

Application of a multivariate technique to Raman spectra for quantification of body chemicals

Raman spectroscopy is a highly specific technique for the identification of molecules by way of the associated characteristic spectra. The aim of this feasibility study is to assess the combination of the multivariate calibration technique of partial least-squares with Raman spectroscopy for the estimation of glucose, lactic acid, and urea concentrations in the presence of each other in a water substrate. The instrument is a CCD-based Raman spectrometer utilizing the 514.5 nm argon laser line. The estimates for the analyte concentrations yielded a standard deviation of concentration residuals of 20.71 mg/dL for glucose, 12.92 mg/dL for lactic acid, and 19.97 mg/dL for urea.<<ETX>>

Noninvasive glucose sensing utilizing a digital closed-loop polarimetric approach

A polarimetric glucose sensor utilizing a digital closed-loop controller was designed and implemented during this study. Its potential as a noninvasive glucose sensor was evaluated in vitro for both glucose doped water and bovine aqueous humor mediums. A physiological hyperglycemic concentration range was used in both calibration and validation of each set of experiments. Ideally, the end application of this system could estimate blood glucose concentrations indirectly by measuring the amount of rotation of a light beams polarization state after it propagates through the aqueous humor contained within the anterior chamber of the eye. The polarimeter designed in this study differs from similar investigated systems in that it utilizes a digital closed-loop control system. This type of controller was implemented in order to further improve system repeatability and stability without sacrificing accuracy. Unique to this investigation, independent validation sets other than those used to create each respective calibration model were obtained. The results of the glucose-doped water experiments yielded mean standard errors of prediction for calibration and validation of 6.91 and 8.84 mg/dl, respectively. The mean standard errors of prediction during calibration and validation of the glucose-doped aqueous humor experiments were higher at 27.20 and 27.47 mg/dl, respectively, due to medium degradation over time while exposed to air.