Functionalised organic field-effect transistors as biosensors for circulating-tumour DNA detection
File(s)
Author(s)
Patrick, Ijeoma
Type
Thesis
Abstract
This thesis describes work towards the development of an organic field-effect transistor biosensor prototype for breast cancer circulating-tumour DNA detection. The work begins with characterisation of the underlying devices, describing the fabrication of bottomgate bottom-contact organic field-effect transistor arrays in-house, using microfabrication processes. Commercially-bought silicon substrates were primarily adopted in combination with an automatic, high-throughput, organic semiconductor dispensing system and molecular additive formulations, to optimise the performance of the bare device array. Dispensed organic semiconductor films exhibited lower performance in devices compared to spin coated films, in terms of a lower mobility and ON/OFF ratio. However, devices formed with dispensed films exhibited low inter-device variation. Additionally, a molecular additive (2,3,5,6-Tetrafluoro-7,7,8,8-tetracyanoquinodimethane, F4-TCNQ) was shown to have the most stabilising effect on devices among the additives screened. Towards sensor fabrication, a novel biofunctionalisation strategy was developed. A semiconducting polymer was synthetically modified to generate reactive azide groups on the molecular backbone, that were subsequently used to covalently bind biorecognition elements through click chemistry. This was demonstrated to be successful in covalently-binding polyethylene glycol groups, biotin molecules and nucleic acid sequences, directly to the conjugated polymer surface, which was confirmed using a combination of surface analysis techniques. A treptavidin-biotin proof-of-concept system was employed to validate the BioFET sensing capability. Detection of streptavidin using biotin-functionalised OFETs was achieved spanning several orders of magnitude, with a high fM limit of detection. The thesis concludes with work towards the detection of a nucleic acid sequence associated with a prevalent breast cancer mutation. Through measuring shifts in the threshold voltage parameter, detection of the single-stranded DNA probe mobilisation and the subsequent sensing of 100 nM of the complementary target sequence was achieved. The level of non-specific interactions was evaluated and the selectivity was assessed using base pair mismatch sequences from the target.
Version
Open Access
Date Issued
2023-01-14
Date Awarded
01/08/2023
License URL
Advisor
Thesis, Molly
Publisher Department
Materials
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)