AbstractThe detection and quantification of biologically important blood analytes plays a crucial role in the screening, diagnosis and management of disease. However the extraction of blood using hypodermic needles brings with it a plethora of issues. Two million cases of needle stick injuries in healthcare staff occur annually and approximately 10% of adults have needle phobia. Microneedles (MNs) have demonstrated potential in the extraction of interstitial fluid (ISF) in a minimally invasive manner due to their short length, thus avoiding stimulating pain receptors in the skin. ISF contains many of the same analytes that are found in the blood including glucose, which is critical in the management of diabetes. However, a large proportion of diabetics do not measure their blood glucose levels as often as recommended due to the pain and inconvenience of conventional methods. Therefore, there is great potential for a minimally invasive MN based approach in the extraction and determination of the concentration of glucose within the ISF to increase patient compliance and mitigate the negative effects of chronic hyperglycaemia.
Chapter 1 discusses the history of blood diagnostics with a focus on the detection of hyperglycaemia in diabetes. The negative consequences of chronic hyperglycaemia and the issues with conventional blood glucose determination are discussed. The potential of MNs to overcome these issues through indirect measurement of blood analytes by sampling ISF is introduced.
Chapter 2 details the materials and methods used in the experimental chapters. Hydrogel forming MNs made from crosslinked polymers have previously demonstrated their ability to withdraw ISF containing glucose in human studies.
Chapter 3 investigates improving the swelling capability of these hydrogel MNs by including sodium carbonate in the formulation. A colorimetric glucose sensor is developed based on glucose oxidase, horseradish peroxidase and a colour forming dye. This sensor is then interfaced with the hydrogel MNs, initially in a hydrogel backplate and successfully demonstrates a visually apparent colour change in response to the extraction of glucose in simulated ISF in vitro. The time taken for the 18 colour change to occur is substantially decreased by embedding the sensor in a paper based backplate and increasing the length of the MN projections.
Chapter 4 involves the fabrication of a single hollow MN device that can successfully withdraw simulated ISF extremely rapidly through capillary action. This device was then coupled to the paper based glucose sensor used in Chapter 3. A method to quantify the intensity of the colour change on the sensor backplate is developed and optimisation of the sensor to produce a linear colour change in response to glucose concentration is successfully carried out, thus increasing its potential as diagnostic point of care (POC) tool.
Chapter 5 addresses some of the limitations of the device in Chapter 4 through the production of a single metal hollow MN device with a silicone housing that aids the flow of fluid from the MN tip and into the paper based sensor backplate through suction. The sensor backplate is also modified with an antioxidant to produce an “OFF-ON” signal response for the detection of hyperglycaemia within the simulated ISF.
Finally, Chapter 6 contains the conclusions of the results chapters and discusses opportunities for further work.
|Date of Award||Jan 2019|
|Sponsors||Norbrook Laboratories Ltd|
|Supervisor||Bridgeen Callan (Supervisor) & John Callan (Supervisor)|
- Interstitial Fluid