Date of Graduation

12-2021

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Chemistry (PhD)

Degree Level

Graduate

Department

Chemistry & Biochemistry

Advisor/Mentor

Paul, David W.

Committee Member

Durham, Bill

Second Committee Member

Stenken, Julie A.

Third Committee Member

Fritsch, Ingrid

Keywords

diabetes mellitus; glucose monitoring; glucose sensitivity; hydrogen peroxide; microelectrode arrays (MEA); oxygen; photolithography; sensor

Abstract

Glucose sensors are very important for detecting blood glucose both in vitro and in vivo. First-generation glucose biosensors were based on the glucose oxidase (GOx) enzyme using molecular oxygen as the electron acceptor and therefore oxygen dependent. Unfortunately for in-vivo work, oxygen in the body is variable and limited. Alternative approaches to overcome the oxygen dependency came with their own limitations. The widely used and commercially available ex-vivo glucose test strip uses a mediator in place of oxygen to free it from oxygen dependency. The mediator-based technology, in most cases cannot be transferred to in vivo applications due to the leaching-out of the toxic mediator. The present in vivo sensors use additional film coatings over the sensor to restrict glucose from reaching the sensor surface while allowing oxygen to pass. The technique succeeds in presenting oxygen in excess to the glucose at the sensor’s surface but at a loss in sensitivity, and precision. This work investigates the construction and optimization of first-generation GOx sensors on both platinum and gold macro and microelectrodes. It addresses an alternative approach to the oxygen-dependency of first-generation sensors by supplying oxygen from an electrode within micro-range proximity to the glucose sensor. The additional oxygen is provided by water electrolysis by poising an oxygen generating electrode at a high positive potential. During this development, the stability of microband electrodes at such high positive potentials was discovered to depend upon the electrode materials and construction. This included gold and platinum MEAs fabrication, and effects of various adhesion metals (chromium, titanium) and contact metal (gold, platinum) properties on the sustainability towards oxygen evolution reaction (OER) voltage. Despite what appeared to be a straightforward approach, the action of the generator actually reduced the glucose signal (derived from the oxidation of enzymatically produced peroxide) at the sensor electrode. This led to numerous experiments and to the conclusion that the action of the oxygen generator produced oxygen but also consumed the glucose signal derived from peroxide oxidation. Different solutions were proposed and demonstrated in this dissertation. The success of this work provides a highly sensitive glucose sensor superior to existing technology for in-vivo applications, and a solution to in vivo sensing by electrochemically supplying the natural and harmless mediator- oxygen. Areas of application of this technique include glucose monitoring under hypoxic conditions such as in tumors, brain, or areas where oxygen is insufficient compared to glucose concentrations.

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