Personalised medicine is widely considered to be the future of global healthcare, where diagnosis, treatment, and potentially even drug development, will become specific to, and optimised for, each individual patient. Traditional population based cell studies suppress the influence of outlier cells that are frequently those of most clinical relevance. Hence single-cell analysis is becoming increasingly important in understanding disease, aiding diagnosis and selecting tailored treatment; but remains the preserve of biomedical laboratories far from the patient. Current instruments depend upon cell-labelling to identify the cell type(s) of interest, which require that these be chosen a-priori and may not be those most clinically relevant. Furthermore, cell-labelling is fundamentally subjective, requiring highly-skilled operators to decide upon the validity of each and every test. Therefore, new test methods need to be developed to enable the widespread adoption of single-cell analysis. The passive electrical properties of biological cells are known to be indicative of the specific cell type, but no technology has demonstrated their comprehensive measurement within a mass-manufacturable device. This work aims to show that biologically meaningful information can be obtained in the form of identifiable “cell signatures” through broadband frequency measurements spanning 100 kHz to 100 MHz that exploit the properties of differential electric fields. This hypothesis is tested through the design, implementation and experimental testing of a dedicated microsystem that integrates two novel designs of electrical sensor within a standard, mass-manufacturable Complementary Metal-Oxide Semiconductor microelectronics technology. One sensor measures the absolute electrical environment above a single sense electrode. The other measures the difference in electrical environment between a pair of electrodes, with view to provide information regarding the suspended cell only, through rejecting the common signal due to its suspending medium. Both sensors are shown capable of detecting individual biological cells in physiological solution, and the differential sensor capable of identifying individually-fixed red blood cells, cervical cancer HeLa cells, and three diameters of homogeneous polystyrene micro-beads of comparable size, all while suspended in physiological saline. These results confirm the hypothesis that differential electric fields provide greater distinction of suspended cells from their environment than existing electrical methods. This finding shows that electrode polarisation arising from proximity to liquids, and particularly physiological media, can be overcome through fully-differential electrical cell sensing. However, misalignment between cells and sensor electrodes limits the sensitivity achieved with the microsystem. Methods to overcome such alignment issues should be investigated in future work, along with higher frequency measurements beyond those presented here.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:738905 |
| Date | January 2017 |
| Creators | Muir, Keith Ross |
| Contributors | Henderson, Robert ; Walton, Anthony ; Renshaw, David |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/28879 |
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