Abstract
Dementia describes a syndrome or group of symptoms associated with the decline of brain functioning such as loss of memory, mood, judgment, language, thinking speed, mental sharpness and other mental abilities. Different classes of Dementia are Jakob Disease, Korsakoff Syndrome, Vascular dementia, Parkinson’s disease, Huntington disease, young onset dementia, Alzheimer’s disease (AD) etc.At present, AD is irreversible and incurable, and it worsens overtime, it is neurodegenerative, caused by the accumulation or build-up of abnormal protein in the brain. It is a type of dementia that is common, affecting about 60% of patients with dementia diagnosis. Globally, over 54 million people are currently affected by dementia, these numbers will rise to 130 million people by 2050, and it is estimated that approximately 9.9 million people will be affected by the disease annually.
Some estimates suggest that managing dementia costs the global healthcare system about $1-2 trillion annually, which is over 1% of global GDP. In the UK, diagnosis, treatment, and care of patients cost the NHS £16 billion annually. These figures do not reflect the true cost and how much impact the disease has on the patient personally, the patient’s family, and society.
Cardiovascular Disease is a name used to describe several illnesses or disorders affecting the heart and the blood vessels. It can also be linked to the accumulation of deposits of fat in the arteries, and damage to arteries in the eyes, kidneys, brain, and heart. The different groups of cardiovascular diseases are deep vein thrombosis, cerebrovascular disease, coronary heart disease, rheumatic heart disease, and many others. Cardiovascular disease is now the world’s major cause of mortality, in 2019, it was estimated that 17.9 million (32%) of all global deaths were linked to cardiovascular diseases, and 85% were due to stroke and heart attack.
The demand and urgency are rising for a portable, low-cost, accurate and rapid system for diagnosis and early detection of these diseases, so that they can be managed and prevented before they become irreversible.
This research involves developing an ultrasensitive and label-free Graphene Field-Effect Transistor (GFET) biosensors that are able to detect different disease biomarkers. The biosensor can detect different biomolecules such as DNA (Deoxyribonucleic Acid) and Protein, specific to neurodegeneration, such as Alzheimer’s and cardiovascular diseases. The biosensors reported in this thesis were fabricated through processes of metal lift-off techniques and photolithographic patterning to create the Graphene channels, voltage electrodes, the drain and source electrodes. The devices were electrically characterized using a 4-probe method with both direct current (DC) and Radiofrequency (RF) Impedance measurements. The devices were optimized by thermal annealing before they were functionalized by a process of immobilizing the Graphene surface of the devices with anti-Clusterin and anti-Troponin antibodies to be able to detect Clusterin (Alzheimer’s Disease biomarker) and Troponin I (biomarker for cardiovascular disease known as Acute Myocardial Infarction). The devices have shown sensitivity, repeatability, and selectivity with an extremely low limit of detection (LoD) of 300 fg/mL exploring the DC technique and 400 fg/mL for the RF technique for Clusterin detection and 328 fg/mL for DC technique and 378 fg/mL for the RF technique for Troponin I detection.
The fabricated GFET biosensors are completely generic and can also potentially be used for a variety of other applications for detection of diseases such as cancer, Parkinson’s etc, and can also be used in a multiplexed platform to enable simultaneous detection of multiple disease biomarkers.
| Date of Award | 2025 |
|---|---|
| Original language | English |
| Supervisor | Shakil Awan (Director of Studies (First Supervisor)), Toby Whitley (Other Supervisor) & Paul Davey (Other Supervisor) |