Browsing by Subject "glucose sensor"
Now showing 1 - 3 of 3
Results Per Page
Sort Options
Item Development of a "Self-Cleaning" Encapsulation Technology for Implantable Glucose Monitoring(2011-02-22) Gant, Rebecca M.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.Item Enhancement of the Response Range and Longevity of Microparticle-based Glucose Sensors(2011-08-08) Singh, SaurabhLuminescent microspheres encapsulating glucose oxidase and an oxygensensitive lumophore have recently been reported as potential implantable sensors for in vivo glucose monitoring. However, there are two main issues that must be addressed for enzymatic systems such as these to realize the goal of minimally-invasive glucose monitoring. The first issue is related to the short response range of such sensors, less than 200 mg/dL, which must be extended to cover the full physiological range (0-600 mg/dL) of glucose possible for diabetics. The second issue is concerning the short operating lifetime of these systems due to enzyme degradation (less than 7 days). Two approaches were considered for increasing the range of the sensor response; nanofilm coatings and particle porosity. In the first approach, microparticle sensors were coated with layer-by-layer deposited thin nanofilms to increase the response range. It was observed that, a precise control on the response range of such sensors can be achieved by manipulating different characteristics (e.g., thickness, deposition condition, and the outermost capping layer) of the nanofilms. However, even with 15 bilayers of poly(allylamine hydrochloride)/poly(styrene sulfonate) (PAH/PSS) nanofilm, limited range was achieved (less than 200 mg/dL). By performing extrapolation on the data obtained for the experimentally-determined response range versus the number of PAH/PSS bilayers, it was predicted that a nanofilm coating comprising of more than 60 PAH/PSS bilayers will be needed to achieve a linear response up to 600 mg/dL. Using modeling, it was realized that a more effective method for achieving a linear response up to 600 mg/dL is to employ microparticles with higher porosity. Sensors were prepared from highly porous silica microparticles (diameter = 7 mu m, porosity = 0.6) and their experimental response was determined. Not surprisingly, the experimentally determined response range of such sensors was found to be higher than 600 mg/dL. To improve the longevity of these sensors, two approaches were employed; incorporation of catalase and increasing the loading of glucose oxidase. Catalase was incorporated into microparticles, which protects the enzyme from peroxide-mediated deactivation, and thus improves the stability of such sensors. Sensors incorporating catalase were found to ~5 times more stable than the GOx-only sensors. It was theoretically predicted, that by maximizing the loading of glucose oxidase within the microparticles, the longevity of such sensors can be substantially improved. Based on this understanding, sensors were fabricated using highly porous microparticles; response range did not vary even after one month of continuous operation under normal physiological conditions. Modeling predicts that 1 mM of glucose oxidase and 1 mM of catalase would extend the operating lifetime to more than 90 days.Item Novel In Situ-Gelling, Alginate-based Composites for Injectable Delivery: Tuning Mechanical and Functional Characteristics(2014-07-24) Roberts, Jason RichardThe development of fully-implantable therapeutic and diagnostic devices represents a new paradigm in biomedical device design. However, designing materials that can perform as injectable matrices for the delivery of sensing and therapeutics chemistries while retaining control over sensor and drug release behaviors is a complex problem. The novel material described herein, microporous alginate composite (MPAC), allows for controllable in situ gelation?and hence enables injection?as well as encapsulation of functional elements such as sensing chemistries or therapeutics. As this material has never been described before, individual component materials, bulk mechanical and gelation properties, and sensing composite response characteristics were examined. The use of polyelectrolyte multilayers (PEMs) in fabrication of MPACs resulted in a porous composite in which macromolecules and nanoparticles were retained within the pores, while allowing for free movement of these materials. Entrapped enzyme molecules were shown to react with diffusing substrates from outside the matrix, confirming the ability of materials from within the pores to interact with small molecules in the local environment. Increasing numbers of PEMs used in composite fabrication was found to result in increased gelation times of hydrogels, while increasing particle concentration reduced gelation times. Changes in pH during MPAC gelation was also dependent on microsphere concentration and PEM numbers. After gelation, MPAC hydrogels immersed in water displayed complex swelling and stiffening behavior dependent on particle concentration and PEM numbers. Oxygen-sensing MPAC hydrogels displayed minor PEM-dependent behavior, while glucose-sensing MPAC hydrogels displayed strong dependence on concentration and PEM numbers. As concentrations increased, sensitivities increased and analytical ranges decreased indicating cooperative behavior among enzyme-containing pores. Utilizing low permeability nanofilms, sensitivities and ranges of sensors could be modulated based upon the number of layers used in fabrication. The development of this new composite system architecture permits an added level of control over injectable hydrogel physical and functional properties such as gelation time and sensor response characteristics. This added control could broaden the usage of alginate as an injectable material and lead to the development of a wide variety of new functional injectable devices.