Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.794340
Title: Multiplexed biosensors for drug discovery applications
Author: Jha, Jahnavi
ISNI:       0000 0004 8499 4486
Awarding Body: University of Bath
Current Institution: University of Bath
Date of Award: 2019
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Abstract:
The phosphorylation of proteins, catalysed by protein kinases, play an important role in nearly every aspect of cell life. The abnormal phosphorylation of proteins is responsible for the onset of several diseases and disorders including various types of cancers, diabetes, Alzheimer's disease, etc. Therefore, the discovery of protein kinase inhibitors is a major focus of the pharmaceutical companies. Drug discovery today is dominated by number a of processes that require expensive chemicals, fluorescent tags and radio-labelling and can often be time consuming and laborious. Through this research, a new process for the screening of protein kinase inhibitors has been explored. In order to improve the cost effectiveness and efficiency of the process, biosensors have been developed using printed circuit board (PCB) technology and made compatible with commercially available complementary metal oxide semiconductors (CMOS). Designing a REFET structure for biosensing where the reference electrode can be eliminated was the final aim. In this thesis, the techniques which are already in use are reviewed in order to understand their drawbacks and to help improve our design. A sensor array that can fit under the industrially used 96 well microtitre plate has been designed such that the existing techniques of liquid handling for drug discovery can be used. In the first technique an electrolyte-insulator-semiconductor structure is interfaced with a PCB for sensing pH changes associated with phosphorylation, through capacitance versus voltage measurements. Next, organic thin film transistors with gold extended gates have been used to detect charge changes during a phosphorylation reaction. Thin films of evaporated tin oxide and tantalum oxide on a PCB have also been tested as pH sensitive membranes for this reaction. The thin films have been used as extended gates for commercial CMOS circuits and the shift in their drain current versus gate voltage characteristics have been measured. The REFET structure has been finally designed with tin oxide as the sensing layer. The reference layer has been designed using a thin film made of SU-8 photoresist as a pH insensitive layer. The two thin films have been used as extended gates to a commercially available matched pair CMOS integrated circuit and a differential measurement in their drain current for a fixed gate voltage is conducted for the phosphorylation reaction. Finally, array of REFET structures are multiplexed for the possibility of high throughput screening. The final device provides an excellent starting point for fabricating sensor arrays compatible with the widely accepted well plate structure and associated liquid handling systems.
Supervisor: Di Lorenzo, Mirella ; Estrela, Pedro Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.794340  DOI: Not available
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