Surface acoustic wave streaming in a PDMS microfluidic system: effect of frequency and fluid geometry & A remote ultrasonic glucose sensor

This thesis describes two separate projects. The first is a theoretical and experimental investigation of surface acoustic wave streaming in microfluidics. The second is the development of a novel acoustic glucose sensor. A separate abstract is given for each here. Optimization of acoustic streaming in microfluidic channels by SAWs Surface Acoustic Waves, (SAWs) actuated on flat piezoelectric substrates constitute a convenient and versatile tool for microfluidic manipulation due to the easy and versatile interfacing with microfluidic droplets and channels. The acoustic streaming effect can be exploited to drive fast streaming and pumping of fluids in microchannels and droplets (Shilton et al. 2014; Schmid et al. 2011), as well as size dependant sorting of particles in centrifugal flows and vortices (Franke et al. 2009; Rogers et al. 2010). Although the theory describing acoustic streaming by SAWs is well understood, very little attention has been paid to the optimisation of SAW streaming by the correct selection of frequency. In this thesis a finite element simulation of the fluid streaming in a microfluidic chamber due to a SAW beam was constructed and verified against micro-PIV measurements of the fluid flow in a fabricated device. It was found that there is an optimum frequency that generates the fastest streaming dependent on the height and width of the chamber. It is hoped this will serve as a design tool for those who want to optimally match SAW frequency with a particular microfluidic design. An acoustic glucose sensor Diabetes mellitus is a disease characterised by an inability to properly regulate blood glucose levels. In order to keep glucose levels under control some diabetics require regular injections of insulin. Continuous monitoring of glucose has been demonstrated to improve the management of diabetes (Zick et al. 2007; Heinemann & DeVries 2014), however there is a low patient uptake of continuous glucose monitoring systems due to the invasive nature of the current technology (Ramchandani et al. 2011). In this thesis a novel way of monitoring glucose levels is proposed which would use ultrasonic waves to ‘read’ a subcutaneous glucose sensitive-implant, which is only minimally invasive. The implant is an acoustic analogy of a Bragg stack with a ‘defect’ layer that acts as the sensing layer. A numerical study was performed on how the physical changes in the sensing layer can be deduced by monitoring the reflection amplitude spectrum of ultrasonic waves reflected from the implant. Coupled modes between the skin and the sensing layer were found to be a potential source of error and drift in the measurement. It was found that by increasing the number of layers in the stack that this could be minimized. A laboratory proof of concept system was developed using a glucose sensitive hydrogel as the sensing layer. It was possible to monitor the changing thickness and speed of sound of the hydrogel due to physiological relevant changes in glucose concentration.

Utility and safety of invasive (fractional flow reserve) and non-invasive (cardiac magnetic resonance imaging) diagnostic tests in patients with NSTEMI

A prospective randomised controlled clinical trial of treatment decisions informed by invasive functional testing of coronary artery disease severity compared with standard angiography-guided management was implemented in 350 patients with a recent non-ST elevation myocardial infarction (NSTEMI) admitted to 6 hospitals in the National Health Service. The main aims of this study were to examine the utility of both invasive fractional flow reserve (FFR) and non-invasive cardiac magnetic resonance imaging (MRI) amongst patients with a recent diagnosis of NSTEMI. In summary, the findings of this thesis are: (1) the use of FFR combined with intravenous adenosine was feasible and safe amongst patients with NSTEMI and has clinical utility; (2) there was discordance between the visual, angiographic estimation of lesion significance and FFR; (3). The use of FFR led to changes in treatment strategy and an increase in prescription of medical therapy in the short term compared with an angiographically guided strategy; (4) in the incidence of major adverse cardiac events (MACE) at 12 months follow up was similar in the two groups. Cardiac MRI was used in a subset of patients enrolled in two hospitals in the West of Scotland. T1 and T2 mapping methods were used to delineate territories of acute myocardial injury. T1 and T2 mapping were superior when compared with conventional T2-weighted dark blood imaging for estimation of the ischaemic area-at-risk (AAR) with less artifact in NSTEMI. There was poor correlation between the angiographic AAR and MRI methods of AAR estimation in patients with NSTEMI. FFR had a high accuracy at predicting inducible perfusion defects demonstrated on stress perfusion MRI. This thesis describes the largest randomized trial published to date specifically looking at the clinical utility of FFR in the NSTEMI population. We have provided evidence of the diagnostic and clinical utility of FFR in this group of patients and provide evidence to inform larger studies. This thesis also describes the largest ever MRI cohort, including with myocardial stress perfusion assessments, specifically looking at the NSTEMI population. We have demonstrated the diagnostic accuracy of FFR to predict reversible ischaemia as referenced to a non-invasive gold standard with MRI. This thesis has also shown the futility of using dark blood oedema imaging amongst all comer NSTEMI patients when compared to novel T1 and T2 mapping methods.