Synthesis, fabrication and characterisation of zinc oxide nanostructures for biomimetic, drug delivery and biosensing applications
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Date
10/07/2017Item status
Restricted AccessEmbargo end date
31/12/2100Author
Syed, Atif
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Abstract
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.