Diabetes Mellitus is a common chronic disease that is an ever-increasing public health issue. Continuous glucose monitoring has been shown to help diabetes mellitus patients stabilize their glucose levels, leading to improved patient health. Hence, a glucose sensor, capable of continuous real-time monitoring, has been a topic of research for three decades. Current methods of glucose monitoring, however, require taking blood samples several times a day, hence patient compliance is an issue. Optical methods are one of the painless and promising methods that can be used for blood glucose predictions. However, having accuracies lower than what is acceptable clinically has been a major concern. To improve on the accuracy of the predictions, the signal-to-noise ratio in the spectrum can be increased, for which the use of thermally tunable vertical cavity surface emitting lasers (VCSELs) as the light source to obtain blood absorption spectra, along with a multivariate technique (Partial Least Square (PLS) techniques) for analysis, is proposed. VCSELs are semiconductor lasers with small dimensions and low power consumption, which makes them suitable for implants. VCSELs provide higher signal-to-noise ratio as they have high power spectral density and operate within a small spectrum. In the current research, experiments were run for the preliminary investigations to demonstrate the feasibility of the proposed technique for glucose monitoring. This research involves preliminary investigations for developing a novel optical system for accurate measurement of glucose concentration. Experiments in aqueous glucose solutions were designed to demonstrate the feasibility of the proposed technique for glucose monitoring. In addition, multivariate techniques, such as PLS, were customized for various specific purposes of this project and its preliminary investigation. This research will lead to the development of a small, low power, implantable optical sensor for diabetes patients, which will be a major breakthrough in the area of treating diabetes patients, upon successful completion of this research and development of the device.

Diabetes Mellitus is a common chronic disease that is an ever-increasing public health issue. Continuous glucose monitoring has been shown to help diabetes mellitus patients stabilize their glucose levels, leading to improved patient health. Hence, a glucose sensor, capable of continuous real-time monitoring, has been a topic of research for three decades. Current methods of glucose monitoring, however, require taking blood samples several times a day, hence patient compliance is an issue. Optical methods are one of the painless and promising methods that can be used for blood glucose predictions. However, having accuracies lower than what is acceptable clinically has been a major concern. To improve on the accuracy of the predictions, the signal-to-noise ratio in the spectrum can be increased, for which the use of thermally tunable vertical cavity surface emitting lasers (VCSELs) as the light source to obtain blood absorption spectra, along with a multivariate technique (Partial Least Square (PLS) techniques) for analysis, is proposed. VCSELs are semiconductor lasers with small dimensions and low power consumption, which makes them suitable for implants. VCSELs provide higher signal-to-noise ratio as they have high power spectral density and operate within a small spectrum. In the current research, experiments were run for the preliminary investigations to demonstrate the feasibility of the proposed technique for glucose monitoring. This research involves preliminary investigations for developing a novel optical system for accurate measurement of glucose concentration. Experiments in aqueous glucose solutions were designed to demonstrate the feasibility of the proposed technique for glucose monitoring. In addition, multivariate techniques, such as PLS, were customized for various specific purposes of this project and its preliminary investigation. This research will lead to the development of a small, low power, implantable optical sensor for diabetes patients, which will be a major breakthrough in the area of treating diabetes patients, upon successful completion of this research and development of the device.

Diabetes Mellitus is a common chronic disease that is an ever-increasing public health issue. Continuous glucose monitoring has been shown to help diabetes mellitus patients stabilize their glucose levels, leading to improved patient health. Hence, a glucose sensor, capable of continuous real-time monitoring, has been a topic of research for three decades. Current methods of glucose monitoring, however, require taking blood samples several times a day, hence patient compliance is an issue. Optical methods are one of the painless and promising methods that can be used for blood glucose predictions. However, having accuracies lower than what is acceptable clinically has been a major concern. To improve on the accuracy of the predictions, the signal-to-noise ratio in the spectrum can be increased, for which the use of thermally tunable vertical cavity surface emitting lasers (VCSELs) as the light source to obtain blood absorption spectra, along with a multivariate technique (Partial Least Square (PLS) techniques) for analysis, is proposed. VCSELs are semiconductor lasers with small dimensions and low power consumption, which makes them suitable for implants. VCSELs provide higher signal-to-noise ratio as they have high power spectral density and operate within a small spectrum. In the current research, experiments were run for the preliminary investigations to demonstrate the feasibility of the proposed technique for glucose monitoring. This research involves preliminary investigations for developing a novel optical system for accurate measurement of glucose concentration. Experiments in aqueous glucose solutions were designed to demonstrate the feasibility of the proposed technique for glucose monitoring. In addition, multivariate techniques, such as PLS, were customized for various specific purposes of this project and its preliminary investigation. This research will lead to the development of a small, low power, implantable optical sensor for diabetes patients, which will be a major breakthrough in the area of treating diabetes patients, upon successful completion of this research and development of the device. / Applied Science, Faculty of / Graduate

To combat diabetes mellitus(DM), a chronicle metabolic disease, from which more than 400 million people suffered in the world, the patients must check the blood glucose level 4-5 times daily with an enzyme-based blood glucose meter and adjust blood glucose levels accordingly. The problem is that enzymatic glucose meters become unstable in the tropics. Therefore, the non-enzymatic method has been urged for blood glucose monitoring, among which the transition metal oxide electrode was found to be promising. However, despite the prolonged effort, its linear detection range is usually much smaller than the glucose level of diabetic patients, calling for an effective solution. Despite many previous attempts, none have solved the problem. Such a challenge has now been conquered by raising the NaOH concentration in the electrolyte, where amperometry, X-ray diffraction, Fourier-transform infrared spectroscopy, and Nuclear magnetic resonance measurements have been conducted. The linear range has been successfully enhanced to 40 mM in 1000 mM NaOH solution, and it was also found that NaOH affected the degree of glucose oxidation, which influenced the current response during sensing. It was expected that the alkaline concentration must be 25 times higher than the glucose concentration to enhance the linear range, much contrary to prior understanding. / Thesis / Candidate in Philosophy

abstract: A noninvasive optical method is developed to monitor rapid changes in blood glucose levels in diabetic patients. The system depends on an optical cell built with a LED that emits light of wavelength 535nm that is a peak absorbance of hemoglobin. As the glucose concentration in the blood decreases, its osmolarity also decreases and the RBCs swell and decrease the path length absorption coefficient. Decreasing absorption coefficient increases the transmission of light through the whole blood. The system was tested with a constructed optical cell that held whole blood in a capillary tube. As expected the light transmitted to the photodiode increases with decreasing glucose concentration. The average response time of the system was between 30-40 seconds. The changes in size of the RBC cells in response to glucose concentration changes were confirmed using a cell counter and also visually under microscope. This method does not allow measuring the glucose concentration with an absolute concentration calibration. It is directed towards development of a device to monitor the changes in glucose concentration as an aid to diabetic management. This method might be improvised for precision and resolution and be developed as a ring or an earring that patients can wear. / Dissertation/Thesis / M.S. Bioengineering 2013

The increasing prevalence of diabetes and the severity of long-term complications have emphasized the need for continuous glucose monitoring. Optically-based methods are advantageous as they have potential for noninvasive or minimally invasive detection. Fluorescence-based affinity assays, in particular, can be fast, reagentless, and highly specific. Poly(ethylene glycol) (PEG) microspheres have been used to encapsulate such fluorescently labeled molecules in a hydrogel matrix for implantation into the body. The matrix is designed to retain the sensing molecules while simultaneously allowing sufficient analyte diffusion. Sensing assays which depend upon a spatial displacement of molecules, however, experience limited motility and diminished sensor response in a dense matrix. In order to overcome this, a process of hydrogel microporation has been developed to create cavities within the PEG that contain the assay components in solution, providing improved motility for large sensing elements, while limiting leaching and increasing sensor lifetime. For an implanted sensor to be successful in vivo, it should exhibit long-term stability and functionality. Even biocompatible materials that have no toxic effect on surrounding tissues elicit a host response. Over time, a fibrous capsule forms around the implant, slowing diffusion of the target analyte to the sensor and limiting optical signal propagation. To prevent this biofouling, a thermoresponsive nanocomposite hydrogel based on poly(N-isopropylacrylamide) was developed to create a self-cleaning sensor membrane. These hydrogels exist in a swollen state at temperatures below the volume phase transition temperature (VPTT) and become increasingly hydrophobic as the temperature is raised. Upon thermal cycling around the VPTT, these hydrogels exhibit significant cell release in vitro. However, the VPTT of the original formula was around 33-34 degrees C, resulting in a gel that is in a collapsed state, ultimately limiting glucose diffusion at body temperature. The hydrogel was modified by introducing a hydrophilic comonomer, N-vinylpyrrolidone (NVP), to raise the VPTT above body temperature. The new formulation was optimized with regard to diffusion, mechanical strength, and cell releasing capabilities under physiological conditions. Overall, this system is a promising method to translate a glucose-sensitive assay from the cuvette to the clinic for minimally invasive continuous glucose sensing.

Regensburg, Univ., Diss., 2008

abstract: This dissertation provides a fundamental understanding of the properties of mesoporous carbon based materials and the utilization of those properties into different applications such as electrodes materials for super capacitors, adsorbents for water treatments and biosensors. The thickness of mesoporous carbon films on Si substrates are measured by Ellipsometry method and pore size distribution has been calculated by Kelvin equation based on toluene adsorption and desorption isotherms monitored by Ellipsometer. The addition of organometallics cobalt and vanalyl acetylacetonate in the synthesis precursor leads to the metal oxides in the carbon framework, which largely decreased the shrink of the framework during carbonization, resulting in an increase in the average pore size. In addition to the structural changes, the introduction of metal oxides into mesoporous carbon framework greatly enhances the electrochemical performance as a result of their pseudocapacitance. Also, after the addition of Co into the framework, the contraction of mesoporous powders decreased significantly and the capacitance increased prominently because of the solidification function of CoO nanoparticles. When carbon-cobalt composites are used as adsorbent, the adsorption capacity of dye pollutant in water is remarkably higher (90 mg/g) after adding Co than the mesoporous carbon powder (2 mg/g). Furthermore, the surface area and pore size of mesoporous composites can be greatly increased by addition of tetraethyl orthosilicate into the precursor with subsequent etching, which leads to a dramatic increase in the adsorption capacity from 90 mg/g up to 1151 mg/g. When used as electrode materials for amperometric biosensors, mesoporous carbons showed good sensitivity, selectivity and stability. And fluorine-free and low-cost poly (methacrylate)s have been developed as binders for screen printed biosensors. With using only 5wt% of poly (hydroxybutyl methacrylate), the glucose sensor maintained mechanical integrity and exhibited excellent sensitivity on detecting glucose level in whole rabbit blood. Furthermore, extremely high surface area mesoporous carbons have been synthesized by introducing inorganic Si precursor during self-assembly, which effectively determined norepinephrine at very low concentrations. / Dissertation/Thesis / Ph.D. Chemical Engineering 2012

Diabetes mellitus is a potentially lethal disease that affects 7.6 percent of American people. In the US, it is recognized as the 6th leading cause of death. Failure to control blood glucose levels (BGL) in patients with either type of diabetes can lead to other serious complications as well, such as loss of limb, blindness and other health problems. Controlling and monitoring the BGL in post-op and intensive care patients in the hospital is also vital to their health. Currently the most reliable method of monitoring BGL is through an invasive procedure which monitors the amount of glucose in blood directly. A non-invasive glucose sensor would drastically improve the treatment of sensitive patients, and serve to improve the quality of diabetic patients' lives. This glucose sensor is strongly based upon the mercury sensor developed by F.E. Hernandez and his colleagues. Glucose is used as a reducing agent to reduce mercury from Hg2+ to Hg0, which will form amalgams with the gold nanorods in solution. The change in aspect ratio of gold nanorods leads to a change in the UV-Visible spectrum of the solution. The blue shift seen was measured and correlated with the glucose concentration of the system. The system was then tested varying conditions such as pH, temperature, gold nanorod concentration, and mercury concentration. A preliminary study of the kinetics of the reaction was also done. The results showed a limit of detection of 1.58x10-13 and a linear dynamic range covering the concentrations of human tear glucose levels that are currently cited in the literature.

Les enregistrements életrophysiologiques ont apporté des informations considérables sur le fonctionnement et le dysfonctionnement du cerveau. Améliorer les dispositifs d'enregistrement permettrait d'approfondir les connaissances au niveau de la science fondamentale et serait bénéfique pour les patients. Les principales limitations des électrodes en contact direct avec le cerveau comprennent leur invasivité, leur biocompatibilité et leur SNR. Il serait aussi souhaitable de mesurer simultanément les signaux électriques et moléculaires. Le couplage entre l'activité électrique et métabolic est encore mal comprise. Le but de ce travail était de fournir des solutions technologiques à ces défis dans le contexte de l’épilepsie.Nous avons développé des grilles flexibles de 4 µm d’épaisseur résolvant les problèmes d’invasivité, de rigidité et de biocompatibilité. Afin d’améliorer le SNR, des sites d'enregistrement en polymère hautement conducteur PEDOT: PSS ont été faits. La qualité des signaux enregistrés in vivo était meilleure que celui obtenu avec de l’or. Puis nous avons validé des sites d'enregistrement en transistors électrochimiques organiques, permettant l'amplification locale des signaux. Les grilles ont été testées in vivo et le SNR a été multiplié par 10. Enfin, nous avons fonctionnalisé les sites avec une enzyme pour mesurer le glucose. Par rapport aux dispositifs classiques, le capteur de glucose a montré une stabilité et une sensibilité inégalée in vitro.En conclusion, l'électronique organique semble être une solution technologique prometteuse pour les limitations des systèmes actuels visant à enregistrer l'activité électrique et moléculaire du cerveau. / Electrophysiological recordings brought considerable information about brain function and dysfunction. Improving recording devices would further our understanding at the basic science level and would be beneficial to patients. Major limitations of current electrodes that are in direct contact with brain tissue include their invasiveness, their poor biocompatibility, their rigidity and a suboptimal signal-to-noise ratio. In addition, it would be desirable to measure simultaneously molecular signals. The coupling between the electrical activity of neurons and metabolism is still poorly understood in vivo. The goal of this work was to provide technological solutions to such challenges in the context of epilepsy. We generate 4 µm thick, totally flexible but resilient grids, thus solving the challenge of invasiveness, rigidity and biocompatibility. In order to improve the signal-to-noise ratio, recording sites were made of the highly conductive polymer PEDOT:PSS. The quality of the in vivo signals recorded was better than that obtained with conventional gold contacts. Going a step further, we made the recording site as an organic electrochemical transistor, which enables local amplification of signals. The grid was tested in vivo and the SNR was increased by a factor of 10. Finally, we functionalized PEDOT:PSS sites with glucose oxidase to measure glucose. Compared to conventional devices, the glucose sensor showed unsurpassed stability and sensitivity in vitro. In conclusion, organic electronics appears to be a promising technological solution to the limitations of current systems designed to record the electrical and molecular activity of the brain.