A successful cancer treatment is a combination of early diagnosis and efficient use of anticancer drugs. There is a chance of approximately 70 - 90% of cancer patients surviving if the diagnosis is conducted early. That means if a diagnosis system is in place which can detect multiple types of cancer at an early stage, a potential cancer therapy is most likely to succeed. However, at present, the available biomedical sensors are unable to detect and differentiate between cancerous cells or tumours. They are also not able to provide continuous real-time monitoring of a patient. Additionally, oral anticancer drugs given during chemotherapy, at the moment, suffer from low bioavailability. Also, a variety of these drugs is not targeted in nature. That means the drug will potentially affect areas of the body which do not need it. The low bioavailability of the drug will not only increase the chemotherapy sessions but also makes the entire process more aggravating for the cancer patient. Therefore, there is an absolute need to have innovative and efficient anticancer drug delivery mechanisms. Finally, current biomedical sensors are primarily made up of silicon (Si) or hard substrates based materials. Even if the biomedical sensor is of a flexible material, the material is either a fragile film or flexible but not stretchable polymers such as polyimide (PI). By having a biomedical sensor which is moderately flexible or not flexible at all, a continuous on-body biomedical sensing is not possible in an efficient manner. That is because hard substrates based biomedical sensors would be difficult to be placed on a body at all times. Furthermore, the flexible biomedical sensors currently suffer from problems such as the electrode on top cracking and damaging after few uses rendering them unusable. Hence, a new fabrication process needs to be devised to solve the issues mentioned above. In this work, an attempt is made to utilise zinc oxide (ZnO) nanostructures for biomedical sensing, drug delivery and biomimetics. ZnO nanostructures are synthesised by using a low-cost wet chemistry process known as hydrothermal growth. Due to the inherent biocompatibility and unique electrical/ piezoelectric properties of ZnO, they acted as prime candidates for the applications outlined above. A high-throughput process is used to synthesise ZnO nanowires (NWs) on Si, polyimide-onsilicon (PI/Si) and directly on PI and polydimethylsiloxane (PDMS) substrates. The work utilises a variety of characterization tools. ZnO nanostructures' morphology is characterised by using a Scanning Electron Microscope (SEM), Transmission Electron Microscope (TEM) and Atomic Force Microscope (AFM). X-ray diffraction (XRD) was used to calculate the crystallite size and the crystalline orientation of the nanostructures. A novel fabrication process is developed to allow direct synthesis and direct patterning of metal electrodes on fully flexible, stretchable and bendable PDMS substrates by using standard photolithography. This novel fabrication process makes the PDMS substrates not expand when exposed to temperatures up to 110 °C. Also; the new fabrication process does not cause the PDMS to swell when exposed to various chemicals such as isopropyl alcohol (IPA) or acetone. The fabrication process has created a new paradigm shift in the field of patterning and producing devices directly on flexible and stretchable substrates. The PDMS substrate is further utilised as a sensitive bovine serum albumin (BSA) protein sensor which is capable of detecting up to femtomolar concentrations in just under 5 min of incubation time. Protein biosensing tests were carried out by measuring the change in resistance at 1V bias voltage. The PDMS based biosensor is tested as a protein sensor because proteins are important biomarkers in cancer diagnosis. Also, protein sensors are immensely useful in the detection of bacteria and viruses thereby allowing further expansion to the technology developed herewith. For the first time, ZnO NWs are used to deliver hydrophobic organic dye, Nile red, in a human body like environment. The Nile red simulates an anticancer drug as they share similar surface chemistry. There is an approximately 80% release of Nile red which shows that ZnO NWs can be used as an efficient anticancer drug delivery system with high bioavailability. For the drug delivery experiments, the dynamic dialysis based release of Nile red (Nr) from the ZnO nanowires is carried out by using UV-Visible (UV-Vis) spectroscopy. Fourier Transform Infrared (FTIR) was used to determine the coordination of Nr across the ZnO nanowires. Finally, a novel synthesis process is used to produce individual ZnO NWs on a single ZnO nanoplate (NP) which are named as ZNWNP nanostructures. ZNWNP nanostructures have high hydrophobicity without the need of any functionalization. The hydrophobicity of the hybrid ZnO nanowires on ZnO nanoplate nanostructures (ZNWNP) is characterised by using contact angle goniometry (CAG). Various contact angle theories have been used to calculate the surface free energy (SFE) of the ZNWNP nanostructures. The high hydrophobicity allows these nanostructures to be used for biomimetic applications such self-cleaning, bioinspired sensors and multimodal biosensing. Additionally, ZNWNP nanostructures can be used in biomedical sensors to create multimodal analysis. The multimodal analysis is immensely useful in cancer detection as at least three or more cancer biomarkers can be used to triangulate the diagnosis. The work presented in the thesis aims to utilise ZnO nanostructures for a variety of biomedical applications. The new fabrication process mentioned above has applications not only in biomedicine but also in the flexible electronics industry. The biomimetic nanostructures combined with the biomedical sensor gives rise to a robust multimodal analysis system which can change the course of the cancer diagnosis. That coupled with the usage of ZnO NWs as an effective anticancer drug delivery system gives an immense promise in advancing cancer therapy as a whole and making the entire treatment process less aggravating and less painful for cancer patients.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:738712 |
| Date | January 2017 |
| Creators | Syed, Atif |
| Contributors | Mastropaolo, Enrico ; Koutsos, Vasileios |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/28735 |
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