Bond rupture is an experimental methodology that is used to augment a conventional mass balance biosensor. A good point-of-care biosensor is fast, reliable, simple, cost-effective, and detects low concentrations of the target analyte. Biosensor development is a multidisciplinary field and bond rupture testing is of technical interest to many groups. The Bond rupture methodology endows a mass probe with the ability to discern bond strength. The recognition of specific bonds by mass loading is separated from erroneous non-specific binding by a probe of the force between the analyte and the transducer. Bond rupture is achieved by acoustic excitation of the point of attachment. The force is incremented gradually until rupture occurs. The advancement of bond rupture biosensors beyond the lab requires improved understanding of the mechanisms of bond rupture by base excitation, the transducers, and the supporting hardware. Bond rupture has traditionally been used in conjunction with the Quartz Crystal Microbalance (QCM). There exists, however, a variety of sensors and transducers to which the bond rupture methodology could be applied. The time, cost and experience required for comprehensive investigation of all avenues is prohibitive. To further the development of bond rupture characteristic experiments are designed and carried out on the QCM platform. Numerical simulations are constructed which model the current bond rupture approach. This work is limited to the simulation of bond rupture by base excitation. From the results of the experimental investigation a number of improvements to the bond rupture technique are proposed. Improvements are tested by simulation and the Surface Acoustic Wave (SAW) device is selected to advance the bond rupture craft. A prototype SAW bond rupture device is designed. The prototype device is manufactured and tested, confirming the principle of SAW bond rupture. Future work is required to progress the SAW bond rupture methodology before possible integration with other sensor systems. Because of this work, and the evaluation of the SAW bond rupture prototype, much is learned about the advancement of SAW device bond rupture.

In patients with aortic stenosis, accurate assessment of severity with echocardiography is central to surgical decision making. But, when image quality is poor or equivocal results obtained, another robust non-invasive technique would be invaluable. Cardiac magnetic resonance (CMR) may be a useful alternative. Phase contrast CMR can measure ow and velocity, therefore it is theoretically possible to estimate the main determinant of severity aortic valve area, using the continuity approach. However, it was found that the phase contrast estimate of stroke volume, sampled in the stenotic jet, systematically underestimated left ventricular stroke volume. This underestimation was greater with increasing aortic stenosis severity. Critical clinical treatment decisions depend on the ability to reliably differentiate between patients with moderate and severe aortic stenosis. To achieve accurate estimation of aortic valve areas the velocity and ow data obtained in these turbulent, high velocity jets must be accurate. In this thesis, non-stenotic and stenotic phantoms were designed and constructed to experimentally interrogate the error. It was determined that signal loss, due to intravoxel dephasing, decreased the reliability of the measured forward ow jet velocities. Extreme signal loss in the jet eventuated in salt and pepper noise, which, with a mean velocity of zero, resulted in the underestimation. Intravoxel dephasing signal loss due to higher order motions, turbulence and spin mixing could all be mitigated by reducing the duration of the velocity sensitivity gradients and shortening the overall echo time (TE). However, improvements in an optimised PC sequence (TE 1:5ms) were not satisfactory. Flow estimates remained variable and were underestimated beyond the aortic valve. To reduce the TE further, a new phase contrast pulse sequence based on an ultrashort TE readout trajectory and velocity dependent slice excitation with gradient inversion was designed and implemented. The new sequence's TE is approximately 25% (0:65ms) of what is currently clinically available (TE 2:8ms). Good agreement in the phantom was maintained up to very high ow rates with improved signal characteristics shown in-vivo. This new phase contrast pulse sequence is worthy of further investigation as an accurate evaluation of patients with aortic stenosis. / This work in this thesis was conducted at The Auckland Bioengineering Institute, The Centre for Advanced MRI and The Oxford Centre for Clinical Magnetic Resonance in collaboration with Siemens Health care.

In patients with aortic stenosis, accurate assessment of severity with echocardiography is central to surgical decision making. But, when image quality is poor or equivocal results obtained, another robust non-invasive technique would be invaluable. Cardiac magnetic resonance (CMR) may be a useful alternative. Phase contrast CMR can measure ow and velocity, therefore it is theoretically possible to estimate the main determinant of severity aortic valve area, using the continuity approach. However, it was found that the phase contrast estimate of stroke volume, sampled in the stenotic jet, systematically underestimated left ventricular stroke volume. This underestimation was greater with increasing aortic stenosis severity. Critical clinical treatment decisions depend on the ability to reliably differentiate between patients with moderate and severe aortic stenosis. To achieve accurate estimation of aortic valve areas the velocity and ow data obtained in these turbulent, high velocity jets must be accurate. In this thesis, non-stenotic and stenotic phantoms were designed and constructed to experimentally interrogate the error. It was determined that signal loss, due to intravoxel dephasing, decreased the reliability of the measured forward ow jet velocities. Extreme signal loss in the jet eventuated in salt and pepper noise, which, with a mean velocity of zero, resulted in the underestimation. Intravoxel dephasing signal loss due to higher order motions, turbulence and spin mixing could all be mitigated by reducing the duration of the velocity sensitivity gradients and shortening the overall echo time (TE). However, improvements in an optimised PC sequence (TE 1:5ms) were not satisfactory. Flow estimates remained variable and were underestimated beyond the aortic valve. To reduce the TE further, a new phase contrast pulse sequence based on an ultrashort TE readout trajectory and velocity dependent slice excitation with gradient inversion was designed and implemented. The new sequence's TE is approximately 25% (0:65ms) of what is currently clinically available (TE 2:8ms). Good agreement in the phantom was maintained up to very high ow rates with improved signal characteristics shown in-vivo. This new phase contrast pulse sequence is worthy of further investigation as an accurate evaluation of patients with aortic stenosis. / This work in this thesis was conducted at The Auckland Bioengineering Institute, The Centre for Advanced MRI and The Oxford Centre for Clinical Magnetic Resonance in collaboration with Siemens Health care.

Global and regional mechanics of the cardiac ventricles were investigated using an anatomicallyaccurate computational model formulated from concise mathematical descriptions ofthe left and right ventricular wall geometries and the non-homogeneous laminar microstructureof cardiac muscle. The finite element method for finite deformation elasticity was developedfor the analysis and included specialised coordinate systems, interpolation schemesand parallel processing techniques for greater computational efficiency.The ventricular mechanics model incorporated the fully orthotropic pole-zero constitutivelaw, based on the three-dimensional architecture of myocardium, to account for the nonlinearmaterial response of resting cardiac muscle, relative to the three anatomically relevant axes.A fibre distribution model was introduced to reconcile some of the pole-zero constitutiveparameters with direct mechanical properties of the tissue (such as the limiting strainsestimated from detailed physiological observations of the collagen helices that surroundmyofibres), whilst other parameters were estimated from in-vitro biaxial tension tests onthin sections of myocardium. A non-invasive approach to in-vivo myocardial materialparameter estimation was also developed, based on a magnetic resonance imaging techniqueto effectively tag ventricular wall tissue.The spatially non-homogeneous distribution of myocardial residual strain was accounted forin the ventricular mechanics model using a specialised growth tensor. A simple model of fluidshift was formulated to account for the changes in local tissue volume due to movement ofintramyocardial blood. Contractile properties of ventricular myofibres were approximatedusing a quasi-static relationship between the fibre extension ratio, intracellular calciumconcentration and active fibre stress, and the framework has been developed to include amore realistic model of active myocardial mechanics, which could be coupled to a realisticdescription of the time-varying spread of electrical excitation throughout the ventricularwalls. Simple volumetric cavity models were incorporated to investigate the effects of arterialimpedance on systolic wall mechanics.Ventricular mechanics model predictions of the cavity pressure versus volume relationships,longitudinal dimension changes, torsional wall deformations and regional distributions ofmyocardial strain during the diastolic filling, isovolumic contraction and ejection phasesof the cardiac cycle showed good overall agreement with reported observations derivedfrom experimental studies of isolated and in-vivo canine hearts. Predictions of the spatialdistributions of mechanical stress at end-diastole and end-systole are illustrated.

In patients with aortic stenosis, accurate assessment of severity with echocardiography is central to surgical decision making. But, when image quality is poor or equivocal results obtained, another robust non-invasive technique would be invaluable. Cardiac magnetic resonance (CMR) may be a useful alternative. Phase contrast CMR can measure ow and velocity, therefore it is theoretically possible to estimate the main determinant of severity aortic valve area, using the continuity approach. However, it was found that the phase contrast estimate of stroke volume, sampled in the stenotic jet, systematically underestimated left ventricular stroke volume. This underestimation was greater with increasing aortic stenosis severity. Critical clinical treatment decisions depend on the ability to reliably differentiate between patients with moderate and severe aortic stenosis. To achieve accurate estimation of aortic valve areas the velocity and ow data obtained in these turbulent, high velocity jets must be accurate. In this thesis, non-stenotic and stenotic phantoms were designed and constructed to experimentally interrogate the error. It was determined that signal loss, due to intravoxel dephasing, decreased the reliability of the measured forward ow jet velocities. Extreme signal loss in the jet eventuated in salt and pepper noise, which, with a mean velocity of zero, resulted in the underestimation. Intravoxel dephasing signal loss due to higher order motions, turbulence and spin mixing could all be mitigated by reducing the duration of the velocity sensitivity gradients and shortening the overall echo time (TE). However, improvements in an optimised PC sequence (TE 1:5ms) were not satisfactory. Flow estimates remained variable and were underestimated beyond the aortic valve. To reduce the TE further, a new phase contrast pulse sequence based on an ultrashort TE readout trajectory and velocity dependent slice excitation with gradient inversion was designed and implemented. The new sequence's TE is approximately 25% (0:65ms) of what is currently clinically available (TE 2:8ms). Good agreement in the phantom was maintained up to very high ow rates with improved signal characteristics shown in-vivo. This new phase contrast pulse sequence is worthy of further investigation as an accurate evaluation of patients with aortic stenosis. / This work in this thesis was conducted at The Auckland Bioengineering Institute, The Centre for Advanced MRI and The Oxford Centre for Clinical Magnetic Resonance in collaboration with Siemens Health care.

Global and regional mechanics of the cardiac ventricles were investigated using an anatomicallyaccurate computational model formulated from concise mathematical descriptions ofthe left and right ventricular wall geometries and the non-homogeneous laminar microstructureof cardiac muscle. The finite element method for finite deformation elasticity was developedfor the analysis and included specialised coordinate systems, interpolation schemesand parallel processing techniques for greater computational efficiency.The ventricular mechanics model incorporated the fully orthotropic pole-zero constitutivelaw, based on the three-dimensional architecture of myocardium, to account for the nonlinearmaterial response of resting cardiac muscle, relative to the three anatomically relevant axes.A fibre distribution model was introduced to reconcile some of the pole-zero constitutiveparameters with direct mechanical properties of the tissue (such as the limiting strainsestimated from detailed physiological observations of the collagen helices that surroundmyofibres), whilst other parameters were estimated from in-vitro biaxial tension tests onthin sections of myocardium. A non-invasive approach to in-vivo myocardial materialparameter estimation was also developed, based on a magnetic resonance imaging techniqueto effectively tag ventricular wall tissue.The spatially non-homogeneous distribution of myocardial residual strain was accounted forin the ventricular mechanics model using a specialised growth tensor. A simple model of fluidshift was formulated to account for the changes in local tissue volume due to movement ofintramyocardial blood. Contractile properties of ventricular myofibres were approximatedusing a quasi-static relationship between the fibre extension ratio, intracellular calciumconcentration and active fibre stress, and the framework has been developed to include amore realistic model of active myocardial mechanics, which could be coupled to a realisticdescription of the time-varying spread of electrical excitation throughout the ventricularwalls. Simple volumetric cavity models were incorporated to investigate the effects of arterialimpedance on systolic wall mechanics.Ventricular mechanics model predictions of the cavity pressure versus volume relationships,longitudinal dimension changes, torsional wall deformations and regional distributions ofmyocardial strain during the diastolic filling, isovolumic contraction and ejection phasesof the cardiac cycle showed good overall agreement with reported observations derivedfrom experimental studies of isolated and in-vivo canine hearts. Predictions of the spatialdistributions of mechanical stress at end-diastole and end-systole are illustrated.

In patients with aortic stenosis, accurate assessment of severity with echocardiography is central to surgical decision making. But, when image quality is poor or equivocal results obtained, another robust non-invasive technique would be invaluable. Cardiac magnetic resonance (CMR) may be a useful alternative. Phase contrast CMR can measure ow and velocity, therefore it is theoretically possible to estimate the main determinant of severity aortic valve area, using the continuity approach. However, it was found that the phase contrast estimate of stroke volume, sampled in the stenotic jet, systematically underestimated left ventricular stroke volume. This underestimation was greater with increasing aortic stenosis severity. Critical clinical treatment decisions depend on the ability to reliably differentiate between patients with moderate and severe aortic stenosis. To achieve accurate estimation of aortic valve areas the velocity and ow data obtained in these turbulent, high velocity jets must be accurate. In this thesis, non-stenotic and stenotic phantoms were designed and constructed to experimentally interrogate the error. It was determined that signal loss, due to intravoxel dephasing, decreased the reliability of the measured forward ow jet velocities. Extreme signal loss in the jet eventuated in salt and pepper noise, which, with a mean velocity of zero, resulted in the underestimation. Intravoxel dephasing signal loss due to higher order motions, turbulence and spin mixing could all be mitigated by reducing the duration of the velocity sensitivity gradients and shortening the overall echo time (TE). However, improvements in an optimised PC sequence (TE 1:5ms) were not satisfactory. Flow estimates remained variable and were underestimated beyond the aortic valve. To reduce the TE further, a new phase contrast pulse sequence based on an ultrashort TE readout trajectory and velocity dependent slice excitation with gradient inversion was designed and implemented. The new sequence's TE is approximately 25% (0:65ms) of what is currently clinically available (TE 2:8ms). Good agreement in the phantom was maintained up to very high ow rates with improved signal characteristics shown in-vivo. This new phase contrast pulse sequence is worthy of further investigation as an accurate evaluation of patients with aortic stenosis. / This work in this thesis was conducted at The Auckland Bioengineering Institute, The Centre for Advanced MRI and The Oxford Centre for Clinical Magnetic Resonance in collaboration with Siemens Health care.

Global and regional mechanics of the cardiac ventricles were investigated using an anatomicallyaccurate computational model formulated from concise mathematical descriptions ofthe left and right ventricular wall geometries and the non-homogeneous laminar microstructureof cardiac muscle. The finite element method for finite deformation elasticity was developedfor the analysis and included specialised coordinate systems, interpolation schemesand parallel processing techniques for greater computational efficiency.The ventricular mechanics model incorporated the fully orthotropic pole-zero constitutivelaw, based on the three-dimensional architecture of myocardium, to account for the nonlinearmaterial response of resting cardiac muscle, relative to the three anatomically relevant axes.A fibre distribution model was introduced to reconcile some of the pole-zero constitutiveparameters with direct mechanical properties of the tissue (such as the limiting strainsestimated from detailed physiological observations of the collagen helices that surroundmyofibres), whilst other parameters were estimated from in-vitro biaxial tension tests onthin sections of myocardium. A non-invasive approach to in-vivo myocardial materialparameter estimation was also developed, based on a magnetic resonance imaging techniqueto effectively tag ventricular wall tissue.The spatially non-homogeneous distribution of myocardial residual strain was accounted forin the ventricular mechanics model using a specialised growth tensor. A simple model of fluidshift was formulated to account for the changes in local tissue volume due to movement ofintramyocardial blood. Contractile properties of ventricular myofibres were approximatedusing a quasi-static relationship between the fibre extension ratio, intracellular calciumconcentration and active fibre stress, and the framework has been developed to include amore realistic model of active myocardial mechanics, which could be coupled to a realisticdescription of the time-varying spread of electrical excitation throughout the ventricularwalls. Simple volumetric cavity models were incorporated to investigate the effects of arterialimpedance on systolic wall mechanics.Ventricular mechanics model predictions of the cavity pressure versus volume relationships,longitudinal dimension changes, torsional wall deformations and regional distributions ofmyocardial strain during the diastolic filling, isovolumic contraction and ejection phasesof the cardiac cycle showed good overall agreement with reported observations derivedfrom experimental studies of isolated and in-vivo canine hearts. Predictions of the spatialdistributions of mechanical stress at end-diastole and end-systole are illustrated.

Global and regional mechanics of the cardiac ventricles were investigated using an anatomicallyaccurate computational model formulated from concise mathematical descriptions ofthe left and right ventricular wall geometries and the non-homogeneous laminar microstructureof cardiac muscle. The finite element method for finite deformation elasticity was developedfor the analysis and included specialised coordinate systems, interpolation schemesand parallel processing techniques for greater computational efficiency.The ventricular mechanics model incorporated the fully orthotropic pole-zero constitutivelaw, based on the three-dimensional architecture of myocardium, to account for the nonlinearmaterial response of resting cardiac muscle, relative to the three anatomically relevant axes.A fibre distribution model was introduced to reconcile some of the pole-zero constitutiveparameters with direct mechanical properties of the tissue (such as the limiting strainsestimated from detailed physiological observations of the collagen helices that surroundmyofibres), whilst other parameters were estimated from in-vitro biaxial tension tests onthin sections of myocardium. A non-invasive approach to in-vivo myocardial materialparameter estimation was also developed, based on a magnetic resonance imaging techniqueto effectively tag ventricular wall tissue.The spatially non-homogeneous distribution of myocardial residual strain was accounted forin the ventricular mechanics model using a specialised growth tensor. A simple model of fluidshift was formulated to account for the changes in local tissue volume due to movement ofintramyocardial blood. Contractile properties of ventricular myofibres were approximatedusing a quasi-static relationship between the fibre extension ratio, intracellular calciumconcentration and active fibre stress, and the framework has been developed to include amore realistic model of active myocardial mechanics, which could be coupled to a realisticdescription of the time-varying spread of electrical excitation throughout the ventricularwalls. Simple volumetric cavity models were incorporated to investigate the effects of arterialimpedance on systolic wall mechanics.Ventricular mechanics model predictions of the cavity pressure versus volume relationships,longitudinal dimension changes, torsional wall deformations and regional distributions ofmyocardial strain during the diastolic filling, isovolumic contraction and ejection phasesof the cardiac cycle showed good overall agreement with reported observations derivedfrom experimental studies of isolated and in-vivo canine hearts. Predictions of the spatialdistributions of mechanical stress at end-diastole and end-systole are illustrated.

Global and regional mechanics of the cardiac ventricles were investigated using an anatomicallyaccurate computational model formulated from concise mathematical descriptions ofthe left and right ventricular wall geometries and the non-homogeneous laminar microstructureof cardiac muscle. The finite element method for finite deformation elasticity was developedfor the analysis and included specialised coordinate systems, interpolation schemesand parallel processing techniques for greater computational efficiency.The ventricular mechanics model incorporated the fully orthotropic pole-zero constitutivelaw, based on the three-dimensional architecture of myocardium, to account for the nonlinearmaterial response of resting cardiac muscle, relative to the three anatomically relevant axes.A fibre distribution model was introduced to reconcile some of the pole-zero constitutiveparameters with direct mechanical properties of the tissue (such as the limiting strainsestimated from detailed physiological observations of the collagen helices that surroundmyofibres), whilst other parameters were estimated from in-vitro biaxial tension tests onthin sections of myocardium. A non-invasive approach to in-vivo myocardial materialparameter estimation was also developed, based on a magnetic resonance imaging techniqueto effectively tag ventricular wall tissue.The spatially non-homogeneous distribution of myocardial residual strain was accounted forin the ventricular mechanics model using a specialised growth tensor. A simple model of fluidshift was formulated to account for the changes in local tissue volume due to movement ofintramyocardial blood. Contractile properties of ventricular myofibres were approximatedusing a quasi-static relationship between the fibre extension ratio, intracellular calciumconcentration and active fibre stress, and the framework has been developed to include amore realistic model of active myocardial mechanics, which could be coupled to a realisticdescription of the time-varying spread of electrical excitation throughout the ventricularwalls. Simple volumetric cavity models were incorporated to investigate the effects of arterialimpedance on systolic wall mechanics.Ventricular mechanics model predictions of the cavity pressure versus volume relationships,longitudinal dimension changes, torsional wall deformations and regional distributions ofmyocardial strain during the diastolic filling, isovolumic contraction and ejection phasesof the cardiac cycle showed good overall agreement with reported observations derivedfrom experimental studies of isolated and in-vivo canine hearts. Predictions of the spatialdistributions of mechanical stress at end-diastole and end-systole are illustrated.