Luminescent 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.
| Identifer | oai:union.ndltd.org:tamu.edu/oai:repository.tamu.edu:1969.1/ETD-TAMU-2010-05-7719 |
| Date | 2010 May 1900 |
| Creators | Singh, Saurabh |
| Contributors | McShane, Michael J. |
| Source Sets | Texas A and M University |
| Language | en_US |
| Detected Language | English |
| Type | thesis, text |
| Format | application/pdf |
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