Abstract
The foundation of most treatments for diseases and illnesses depends on a two-pronged approach: 1) detect these issues as early as possible, and 2) treat them in an effective manner. Early detection and diagnosis has been key in providing beneficial treatments, improving patient survivability and quality of life. As nanotechnology advances, low-dimensional materials have been of interest in a wide spectrum of cell-based biological applications, including the improvement of disease detection and treatments. Their size (nanoscale in one or more dimensions) gives rise to their unique properties, which are advantageous for improving detection sensitivity and therapeutic efficiency. Thus, low-dimensional materials have been harnessed for cell-based applications such as biosensors, bioimaging, tissue-engineering platforms, drug delivery agents and therapeutic agents. Currently, conventional detection systems are limited by invasive, indirect and single cell detection methods, which reduce the reliability and reusability of these systems. Moreover, gold standard treatment methods are burdened with severe side effects and have limited therapeutic efficiency. Low-dimensional materials can bridge the gap to improve the detection of a small population of cells within an adherent heterogenous cell population, and support current methods of treatment to improve therapeutic efficiency. The research in this thesis aims to study the versatility of low-dimensional materials for electrical-based detection and electrothermal ablation of a small population of cells within an adherent heterogenous cell population. The interaction between nanomaterials and different cell types provide a deeper understanding of current flow, and can distinguish between different cell types in an adherent, heterogenous cell population. Currently, few electrical-based detection systems have distinguished different cell types by their small differences in native bioelectrical properties. We hypothesise that this can be achieved with low-dimensional materials due to their exceptional electrical characteristics and unique interactions with different cell types. The research described in this thesis includes the enhancement and iv selective detection of cells using low-dimensional nanomaterials and electrical-based detection methods, and demonstrates electrothermal ablation based on a similar set up. In the first study, we demonstrate a proof of concept electrical based detection method using few-layered two-dimensional molybdenum disulphide (MoS2) nanosheets and currentvoltage (I-V) measurements for the detection of human embryonic stem cells (hESCs, H9 cells). Using molecular dynamics (MD) simulation, the interaction between a generic phosphatidylcholine (POPC) lipid bilayer and MoS2 nanosheet was observed. Favourable covalent and non-covalent interactions were observed between the lipid and the nanosheet. Few-layered MoS2 nanosheets demonstrated low toxic effects with low nanomaterial concentration, and little/no effect on H9 cell pluripotency was observed. The addition of MoS2 nanosheets resulted in an increased peak current with applied voltage, which was not observed for the H9 cells on the device alone. The work in this study demonstrates the use of low dimensional materials to improve the current output range and enhances the current output for H9 cells. Building upon the proof-of-concept method in the first study, human luminal breast cancer (MCF-7) cells were detected with a MoS2 nanosheet and direct current (DC) based system. A lipid bilayer based on a cancer cell membrane was modelled with a MoS2 nanosheet to provide information on the interactions and electrical profile of the cell membrane using MD simulation. Typical characterisation was performed for few-layered MoS2, and the nanosheet demonstrated low cytotoxicity towards MCF-7 cells. Applying a voltage-bias negative DC sweep demonstrated a MoS2-enhanced impedance output for MCF-7 cells incubated with the nanosheet. Furthermore, the MoS2-based sensor was capable of detecting cancer cells with a low detection limit of 3 × 103 cells, lower than previous state-of-the-art electrical-based detection methods. A highly sensitive electrical-based detection system was designed to distinguish cancer cells from its healthy counterpart. Using a carbon nanotube (CNT) photo-assisted alternating current (AC) pulse system, the current signal for MCF-7 cells incubated with CNT was higher than that for healthy breast epithelial (MCF-10A) cells. The system was able to identify as few as 1.5 × 103 MCF-7 cells within a heterogenous cell population, lower than our previous work. MD simulation showed spontaneous interaction between cancer and healthy cell membrane models and CNT, where hydrophobic CNTs embedded themselves within the hydrophobic lipid tails. Due to the differences in lipid composition between the cancer and healthy cell membranes, the CNT appeared to affect the mechanical properties of the lipid bilayer structures, resulting in a more flexible cancer lipid bilayer. The fluidity of the cancer lipid v bilayer could have allowed more CNT to embed itself within the cancer cells, enhancing the current flow upon light exposure and AC pulse application. Building upon this system, we demonstrated cancer cell-specific electrothermal ablation. Due to the unique band gap structure, CNTs possess excellent thermal conductivity that can be activated by electrical pulses. Thermal simulations demonstrated increases in temperatures within the cell layer in the presence of CNT. Using the same AC CNT framework, efficient electrothermal ablation was observed to be cell specific; due to the different cell membrane compositions, CNT uptake was observed to be increased for MCF-7 cells over MCF-10A cells. The CNT-based electrothermal ablation method was capable of causing ~68% of MCF-7 cell death, an improvement over previous heat generating therapies without additional chemotherapeutic drugs. These studies set the foundation for future nanomaterial-based detection and therapeutic devices for clinical applications.