Document Type

Dissertation

Degree

Doctor of Philosophy (PhD)

Major/Program

Electrical Engineering

First Advisor's Name

Shekhar Bhansali

First Advisor's Committee Title

Committee chair

Second Advisor's Name

Nezih Pala

Second Advisor's Committee Title

Committee member

Third Advisor's Name

Shubhendu Bhardwaj

Third Advisor's Committee Title

Committee member

Fourth Advisor's Name

Kingsley Lau

Fourth Advisor's Committee Title

Committee member

Fifth Advisor's Name

Veena Misra

Fifth Advisor's Committee Title

Committee member

Sixth Advisor's Name

Michael Daniele

Sixth Advisor's Committee Title

Committee member

Seventh Advisor's Name

Robert S. Kirsner

Seventh Advisor's Committee Title

Committee member

Keywords

biosensor, wound healing, purine cycle, enzymatic sensing, electrochemical sensor, micro-nano fabrication, wearable sensing

Date of Defense

7-3-2019

Abstract

Wearable biosensing has the tremendous advantage of providing point-of-care diagnosis and convenient therapy. In this research, methods to stabilize the electrochemical sensing response from detection of target biomolecules, Uric Acid (UA) and Xanthine, closely linked to wound healing, have been investigated. Different kinds of materials have been explored to address such detection from a wearable, healing platform. Electrochemical sensing modalities have been implemented in the detection of purine metabolites, UA and Xanthine, in the physiologically relevant ranges of the respective biomarkers. A correlation can be drawn between the concentrations of these bio-analytes and wound severity, thus offering probable quantitative insights on wound healing progression. These insights attempt to contribute in reducing some impacts of the financial structure on the healthcare economy associated with wound-care.

An enzymatic electrochemical sensing system was designed to provide quick response at a cost-effective, miniaturized scale. Robust enzyme immobilization protocols have assisted in preserving enzyme activity to offer stable response under relevant variations of temperature and pH, from normal. Increased hydrophilicity of the sensor surface using corona plasma, has assisted in improving conductivity, thus allowing for increased electroactive functionalization and loading across the substrate’s surface. Superior sensor response was attained from higher loading of nanomaterials (MWCNT/AuNP) and enzymes (UOx/XO) employed in detection.

Potentiometric analyses of the nanomaterial modified enzymatic biosensors were conducted using cyclic voltammetry (CV) and differential pulse voltammetry (DPV) modalities. Under relevant physiological conditions, the biosensor was noted to offer a variation in response between 10 % and 30 % within a week. Stable, reproducible results were obtained from repeated use of the biosensor over multiple days, also offering promise for continuous monitoring. Shelf life of the biosensor was noted to be more than two days with response retained by about 80 % thereafter. Secondary analyses have been performed utilizing the enzymatic biosensor to explore the feasibility of target biomarker detection from clinical extracts of different biofluids for wound monitoring. Biosensor response evaluation from the extracts of human wound exudate, and those obtained from perilesional and healthy skin, provided an average recovery between 107 % and 110 % with a deviation within (+/-) 6 %. Gradual decrease in response (10-20 %) was noted in detection from extracts further away from injury site. Increased accumulation of biofluids on the sensor surface was studied to explore sensor response stability as a function of sample volume. With a broad linear range of detection (0.1 nM – 7.3 mM) and detection limits lower than the physiological concentrations, this study has assessed the viability of stable wound monitoring under physiologically relevant conditions on a wearable platform.

Identifier

FIDC007817

ORCID

0000-0001-5169-8451

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