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Title: Development of a bile acid biosensor for use in the clinical diagnosis of cholestasis
Author: Lawrance, Dominic
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2012
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This thesis describes the development of a disposable, point-of-care biosensor for measurement of total serum bile acids. The condition known as intrahepatic cholestasis of pregnancy was the motivation behind the development of the sensor. Raised serum bile acids in the absence of any liver disorder are an indicator of cholestasis. During pregnancy high bile acid levels are associated with an increased risk of adverse fetal outcomes. Current methods for analysing bile acid levels require samples to be processed by trained personnel with a time to result from hours to days. The aims of this project therefore were to assess the feasibility of an in situ measurement system by which a patient could be diagnosed rapidly and without the need for a laboratory setting. The first chapter presents background information and introduces key areas of relevance to the rest of the thesis. The second chapter outlines all of the materials and methods used in order to obtain the results described herein. The third chapter concentrates on the electrode reaction which forms the basis for detection. The fourth chapter focuses on the development of the biosensor and the key enzymatic reaction which confers specificity to bile acids. The fifth chapter presents clinical results obtained using the biosensor compared with the standard clinical values. The sixth chapter summarises the project and discusses future development and how this research can be utilised. The original contributions to scientific knowledge are: • A disposable biosensor that, unlike other sensors in the literature, is reported working with untreated serum samples to detect bile acids at clinically relevant levels. • A feasibility study demonstrating the use of the biosensor with clinical samples emphasising the expedience of the biosensor as an in situ tool for measurement of serum bile acids. • A previously unreported method for carrying out electrochemical assays involving the standard addition of bile acids to calibrate the biosensor and account for variations in sensitivity.
Supervisor: Williamson, Catherine ; Cass, Tony ; Boutelle, Martyn Sponsor: Shapu Kabushiki Kaisha
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available