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We present a new mechanism for achieving needle free jet injection that significantly reduces the power required to perform a given injection. Our ‘compound ampoule’ produces two phases of jet speed under a constant force input by changing the effective piston area part-way through the injection. In this paper we define the benefits associated with a compound ampoule, relative to those of the conventional single piston design, by developing expressions for the power and energy required to perform an injection. We demonstrate that a compound ampoule can reduce the maximum input power required to perform a jet injection to less than one fifth of that previously required, enabling motors of less than half the mass to perform the same injection. We then detail the development of a prototype compound ampoule injector. Results from testing of this prototype demonstrate the function of a compound ampoule and verify the expected reduction in the required power and energy. Injections into post mortem porcine tissue confirm that our compound ampoule prototype can achieve the delivery of 1 mL of liquid into post-mortem tissue at least as effectively as a conventional ampoule. This approach will advance progress toward light-weight and power-efficient needle-free jet injectors for transdermal drug delivery.

Computer vision and image processing algorithms form essential components of many industrial, medical, commercial, and research-related applications. Modern imaging systems provide high resolution images at high frame rates, and are often required to perform complex computations to process image data. However, in many applications rapid processing is required, or it is important to minimise delays for analysis results. In these applications, central processing units (CPUs) are inadequate, as they cannot perform the calculations with sufficient speed. To reduce the computation time, algorithms can be implemented in hardware accelerators such as digital signal processors (DSPs), field-programmable gate arrays (FPGAs), and graphics processing units (GPUs). However, the selection of a suitable hardware accelerator for a specific application is challenging. Numerous families of DSPs, FPGAs, and GPUs are available, and the technical differences between various hardware accelerators make comparisons difficult. It is also important to know what speed can be achieved using a specific hardware accelerator for a particular algorithm, as the choice of hardware accelerator may depend on both the algorithm and the application. The technical details of hardware accelerators and their performance have been discussed in previous publications. However, there are limitations in many of these presentations, including: inadequate technical details to enable selection of a suitable hardware accelerator; comparisons of hardware accelerators at two different technological levels; and discussion of old technologies. To address these issues, we introduce and discuss important considerations when selecting suitable hardware accelerators for computer vision and image processing tasks, and present a comprehensive review of hardware accelerators. We discuss the practical details of chip architectures, available tools and utilities, development time, and the relative advantages and disadvantages of using DSPs, FPGAs, and GPUs. We provide practical information about state-of-the-art DSPs, FPGAs, and GPUs as well as examples from the literature. Our goal is to enable developers to make a comprehensive comparison between various hardware accelerators, and to select a hardware accelerator that is most suitable for their specific application.

Jet injection presents a promising alternative to needle and syringe injection for transdermal drug delivery. The controllability of recently-developed jet injection devices now allows jet speed to be modulated during delivery, and has enabled efficient and accurate delivery of volumes up to 0.3 mL. However, recent attempts to inject larger volumes of up to 1 mL using the same methods have highlighted the different requirements for successful delivery at these larger volumes. This study aims to establish the jet speed requirements for delivery of 1 mL of liquid using a controllable, voice coil driven injection device. Additionally, the effectiveness of a two-phase jet speed profile is explored (where jet speed is deliberately decreased toward the end of the injection) and compared to the constant jet speed case. A controllable jet injection device was developed to deliver volumes of 1 mL of liquid at jet speeds140 m/s. This device was used to deliver a series of injections into post-mortem porcine tissue in single and two-phase jet speed profiles. Single-phase injections were performed over the range 80 m/s to 140 m/s. Consistent delivery success (80% of the liquid delivered) was observed at a jet speed of 130 m/s or greater. Consistent penetration into the muscle layer coincided with delivery success. Two-phase injections of 1 mL were performed with a first phase volume of 0.15 mL, delivered at 140 m/s, while the injection of the remainder of fluid was delivered at a second phase speed that was varied over the range 60 m/s to 120 m/s. Ten two-phase injections were performed with a second phase speed of 100 m/s producing a mean delivery volume of 0.8 mL ± 0.2 mL, while the single-phase injections at 100 m/s achieved a mean delivery volume of 0.4 mL ± 0.3 mL. These results demonstrate that a reduced jet speed can be used in the later stages of a 1 mL injection to achieve delivery success at a reduced energy cost. We found that a jet speed approaching 100 m/s was required following initial penetration to successfully deliver 1 mL, whereas speeds as low as 50 m/s have been used for volumes of0.3 mL. These findings provide valuable insight into the effect of injection volume and speed on delivery success; this information is particularly useful for devices that have the ability to vary jet speed during drug delivery.

This paper presents a new two-step method for finding two-dimensional translational shifts with subpixel accuracy. This algorithm can measure subpixel shifts, even in images with few features, or in noisy images where many existing algorithms fail. In the first step of the algorithm (the integer part), the noise-robustness of the gradient correlation methods was improved by replacing central difference differentiators with Savitzky–Golay differentiators (SGDs). In the second step of the algorithm (the subpixel part), several modifications have been proposed to increase the accuracy and noise-robustness of phase-based methods for finding subpixel shifts. Moreover, two error metrics were introduced to quantify the output accuracy of the integer and subpixel parts of the algorithm. Comprehensive tests were conducted on 2400 standard 128 pixel × 128 pixel subimages subjected to synthetic shifts and rotations. Tests showed that the accuracy of the proposed method for finding translational shifts is of the order of a few ten-thousandths of a pixel, which is a substantial improvement over other state-of-the-art methods. For the rotation tests, the method outperformed comparable techniques. Furthermore, results showed that the proposed method generally provides better performance than other competing methods when images contained Gaussian or salt and pepper noise. The proposed method can be used in applications where high accuracy, robustness to noise, and/or computation efficiency are important.

This paper addresses some problems of modelling incompressible media using meshfree methods with a stabilised mixed formulation. The aims of this paper are twofold: to avoid the volumetric locking that occurs at the incompressible limit; and to circumvent the inf–sup condition while approximating both displacement and pressure with the same set of nodes and shape functions. We employ a modified polynomial pressure projection stabilisation method to stabilise and filter spurious pressure modes, where the gradient is corrected as proposed by Duan et al. (2014). The gradient correction is used to counteract the lack of variational consistency when numerical integration of the rational shape functions is performed, a threat that could undermine the stabilisation effort. The resulting novel method passes the mixed patch tests, and is demonstrated to be effective and optimally accurate in linear elasticity and Stokes flow test cases.

Abusive head trauma (AHT) is a potentially fatal result of child abuse but the mechanisms of injury are controversial. To address the hypothesis that shaking alone is sufficient to elicit the injuries observed, effective computational and experimental models are necessary. This paper investigates the use of a coupled rigid-body computational modelling framework to reproduce in vivo shaking kinematics in AHT. A sagittal plane OpenSim computational model of a lamb was developed and used to interpret biomechanical data from in vivo shaking experiments. The acceleration of the head during shaking was used to provide in vivo validation of the associated computational model. Results of this study demonstrated that peak accelerations occurred when the head impacted the torso and produced acceleration magnitudes exceeding 200ms(-)(2). The computational model demonstrated good agreement with the experimental measurements and was shown to be able to reproduce the high accelerations that occur during impact. The biomechanical results obtained with the computational model demonstrate the utility of using a coupled rigid-body modelling framework to describe infant head kinematics in AHT.

Fetal head geometry plays an important role in the mechanics of childbirth during the second stage labour. Large heads have been shown to be associated with difficult and prolonged childbirth. However, the relationship between the fetal head geometry and childbirth mechanics has not been quantitatively analysed. To address this, our study used finite element (FE) modelling techniques and biomechanical simulations to analyse the contribution of fetal head shape and size on the mechanics of childbirth. X-ray computed tomography (CT) images from 26 newborn infants (less than 9 days old) without skull abnormalities were used to construct individual-specific FE models of the fetal skull. Simulations of childbirth were conducted using each model of the skull and a customised pelvic floor model based on magnetic resonance imaging (MRI) of a healthy nulliparous woman. The force required for delivery, the maximum principal stresses, and the maximum principal stretch ratios at the left and right pelvic floor muscle-pubic bone interfaces were quantified. Partial least squares regression (PLSR) models for predicting these mechanical indices were constructed using: (i) either the FE geometries of the fetal heads or the biometrical parameters (biparietal diameters and fetal head circumferences) as inputs; and (ii) either a linear or a quadratic function for the inner relation. The predictabilities of the mechanical indices using the PLSR models were quantified using a leave-one-out analysis. Quantitative associations were found between the geometric parameters of the fetal head and the indices of childbirth mechanics. When using the full FE geometries as inputs, the PLSR model using a linear inner relation gave better predictability than the model using a quadratic inner relation. This could be attributed to the quadratic inner relation correlating response to the noise in point-to-point correspondence. When using the biometrical parameters of the skull as inputs, the PLSR model using a quadratic inner relation gave the best overall predictability. Such a model could be implemented in a clinical setting as a predictive model for childbirth planning and as an educational tool for clinical training.

Characterising the mechanical properties of human facial skin is a challenging but important endeavour with applications in biomedicine, surgery simulation, forensics, and animation. Many existing computer models of the face are not based on in vivo facial skin deformation data but rather on experiments using in vitro facial skin or other soft tissues. The facial skin of five volunteers was subjected to a rich set of deformations using a micro-robotic device. The force–displacement response was recorded for each deformation. All volunteers' facial skin exhibited a non-linear, anisotropic, and viscoelastic force–displacement response. We propose a finite element model that simulated the experimental deformations with error-of-fits ranging from 11% to 23%. The skin was represented by an Ogden strain energy function and a quasi-linear viscoelastic law. From non-linear optimisation procedures, we determined material parameters and in vivo pre-stresses for the central cheek area of five volunteers and five other facial points on one volunteer. Pre-stresses ranged from 15.9 kPa to 89.4 kPa.

The VPH/Physiome Project is developing the model encoding standards CellML (cellml.org) and FieldML (fieldml.org) as well as web-accessible model repositories based on these standards (models.physiome.org). Freely available open source computational modelling software is also being developed to solve the partial differential equations described by the models and to visualise results. The OpenCMISS code (opencmiss.org), described here, has been developed by the authors over the last six years to replace the CMISS code that has supported a number of organ system Physiome projects. OpenCMISS is designed to encompass multiple sets of physical equations and to link subcellular and tissue-level biophysical processes into organ-level processes. In the Heart Physiome project, for example, the large deformation mechanics of the myocardial wall need to be coupled to both ventricular flow and embedded coronary flow, and the reaction-diffusion equations that govern the propagation of electrical waves through myocardial tissue need to be coupled with equations that describe the ion channel currents that flow through the cardiac cell membranes. In this paper we discuss the design principles and distributed memory architecture behind the OpenCMISS code. We also discuss the design of the interfaces that link the sets of physical equations across common boundaries (such as fluid-structure coupling), or between spatial fields over the same domain (such as coupled electromechanics), and the concepts behind CellML and FieldML that are embodied in the OpenCMISS data structures. We show how all of these provide a flexible infrastructure for combining models developed across the VPH/Physiome community.

The non-linear, anisotropic, and viscoelastic properties of human skin vary according to location on the body, age, and individual. The measurement of skin's mechanical properties is important in several fields including medicine, cosmetics, and forensics. In this study, a novel force-sensitive micro-robot applied a rich set of three-dimensional deformations to the skin surface of different areas of the arms of 20 volunteers. The force–displacement response of each area in different directions was measured. All tested areas exhibited a non-linear, viscoelastic, and anisotropic force–displacement response. There was a wide quantitative variation in the stiffness of the response. For the right anterior forearm, the ratio of the maximum probe reaction force to maximum probe displacement ranged from 0.44 N mm −1 to 1.45 N mm −1 . All volunteers exhibited similar qualitative anisotropic characteristics. For the anterior right forearm, the stiffest force–displacement response was when the probe displaced along the longitudinal axis of the forearm. The response of the anterior left forearm was stiffest in a direction 20° to the longitudinal axis of the forearm. The posterior upper arm was stiffest in a direction 90° to the longitudinal axis of the arm. The averaged posterior upper arm response was less stiff than the averaged anterior forearm response. The maximum probe force at 1.3 mm probe displacement was 0.69 N for the posterior upper arm and 1.1 N for the right anterior forearm. The average energy loss during the loading–unloading cycle ranged from 11.9% to 34.2%. This data will be very useful for studying the non-linear, anisotropic, and viscoelastic behaviour of skin and also for generating material parameters for appropriate constitutive models.

Calorimeters can be miniaturized to the point where they can be integrated into platforms such as micro-total analysis systems (μTAS) or lab-on-chip. Models of microscale calorimeters currently fail to account for variations of material properties known to be present in thin films. This study attempts to address this deficiency. Resistivity and absolute Seebeck coefficient of gold and nickel thin films were found to vary linearly with the inverse of film thickness in the submicron range. Thin-film thermopiles composed of gold and nickel were fabricated and their resistance and sensitivity were measured. Our results show that thin-film effects can introduce a 15% decrease in sensitivity (temperature-to-voltage conversion ratio) and a 30% decrease in resolution (smallest resolvable temperature difference). Introducing material properties variation with film thickness into models of thermopile performance resulted in improved estimates. Modelling results suggest that grain boundary scattering is a strong contributor to the observed film-thickness-related change of resistivity and Seebeck coefficient. These observations have implications for improving the design and fabrication of thermopile-based, and other microfabricated, microscale calorimeters.

Advances in biotechnology and experimental techniques have lead to the elucidation of vast amounts of biological data. Mathematical models provide a method of analysing this data; however, there are two issues that need to be addressed: (1) the need for standards for defining cell models so they can, for example, be exchanged across the World Wide Web, and also read into simulation software in a consistent format and (2) eliminating the errors which arise with the current method of model publication. CellML has evolved to meet these needs of the modelling community. CellML is a free, open-source, eXtensible markup language based standard for defining mathematical models of cellular function. In this paper we summarise the structure of CellML, its current applications (including biological pathway and electrophysiological models), and its future development—in particular, the development of toolsets and the integration of ontologies.

CellML™ is an exchange fonnat developed by the University of Auckland in collaboration with Physiome Sciences, Inc., for describing the structure and underlying mathematics of biological models. CellML 1.0 has already been used to define electrophysiological, mechanical, signal transduction, and metabolic pathway models. Although CellML 1.0 is sufficient to describe most biological models, the structure is inadequate to support the increasingly complex systems in biology. CellML 1.1 has been developed to extend the component-based architecture of CellML 1.0 to facilitate model expansion and re-use.

In studies of muscle mechanics, the calculation of developed stress is critically dependent on the dynamic change in the geometry of the muscle. However, previous studies have commonly inferred cross-sectional area from measurements of quiescent muscle width. We have constructed a novel instrument to address the issue of ill-defined estimates of stress: arising from inaccurate quantification of geometry. This instrument is capable of measuring the time-varying 3-dimensional geometry of an actively twitching trabecula using optical coherence tomography, while simultaneously measuring force, controlling length, and imaging the muscle using transmission microscopy.We take advantage of these capabilities to show that a representative trabecula, tethered between two hooks and undergoing steady-state, fixed-end twitches at optimal length, had a highly variable spatial distribution of stress, during each twitch. The variability of stress was a minimum during the onset of force development (± 4.2% of the median). At this time, stress along the muscle's length ranged from 81.7% to 114.6% of the median. During the course of a twitch, the variability increased to a maximum (± 9.2% of median stress) which occurred near the end of the descending arm of the force trace. The stress at this time ranged from 84.2% to 136.7% of the median.In addition, at peak force, the calculated volume of the trabecula had increased by 4.6% over resting. The change in apparent volume could be attributed to: movement of the muscle with respect to the hooks, a systematic error in segmentation, or an actual change of volume. This instrument, coupled with our high-speed sarcomere-length imaging system, will be useful in constructing a finite-element model of the tissue to better understand the relationship between stress variation and sarcomere length distribution.

The energetic output of cardiac muscle is closely correlated with its mechanical outputs. Using isolated cardiac preparations (papillary muscles and trabeculae) most investigators have found a linear relation between heat production and developed force, where the heat production at zero force indexes the metabolic cost associated with Ca2+ cycling, predominantly by the sarcoplasmic reticulum Ca2+-ATPase. To our knowledge, the heat-stress relationship of cardiac muscle at physiological temperature has not yet been reported. Thus, it is of paramount important to extend previous studies to determine the heat-stress relation at 37°C.Our flow-through micro-mechano-calorimeter is capable of simultaneously measuring the heat output, length change, and force production of isolated rat cardiac trabeculae, but was restricted to room temperature measurements (22°C). Two modifications to the instrument have been made to allow measurements at physiological temperature. We substituted thermoelectric heat pumps for our thin-film thermopile temperature sensors, thereby reducing light sensitivity and lowering the electrical noise floor. We also added other thermoelectric heat pumps for controlling the temperature of the instrument to a set-point of up to 40°C, with 100 μK resolution. Finite element modelling was used to inform and optimise the choice and position of the heat pumps within the device. The heat-rate resolution of our instrument has thereby been improved ten-fold to 5.8 nW over a 5 Hz bandwidth, corresponding to a temperature change of approximately 0.9 μK.Using the improved calorimeter, we have determined, for the first time, the heat-stress relation of isolated cardiac trabeculae at 37°C. The value of the heat-intercept is at the vicinity of 1.5 kJ m−3 per twitch, which amounts to approximately 25 Ca2+ ions sequestered by the sarcoplasmic reticulum Ca2+-ATPase within a sarcomere with each twitch.

In order to study nature's micro-machine, the muscle cell, we have developed, MR-1, a special purpose micro-motion robot. MR-1 has two limbs which are able to grasp single living muscle cells at each end and perform mechanical and optical experiments on them. An interesting set of system identification, control and modelling problems arise in this work. Traditional approaches to controlling the micro-robot have failed to meet our requirements and in our muscle studies, linear time-invariant system identification methods have not yielded useful scientific insights. In this paper the background to these problems is given together with our attempts to provide solutions to them. In some cases our attempts have been fruitful in others we have only succeeded in defining the problem and so must await future work.