1,721,005 research outputs found
Optimisation of analyte transport in integrated microfluidic affinity sensors for the quantification of low levels of analyte
No full textNew designs for microfluidic channels to be integrated with small-scale affinity sensors for analytical applications are provided. Theoretical approaches demonstrate efficient and uniform mass transfer of the analyte from the bulk flow to small-scale affinity sensors in the base of fluidic channels by (i) active control of the analyte flow speed over the affinity sensor, (ii) non-rectangular channel geometries and (iii) non-uniform distributions of recognition binding sites over the active area of the sensor. The methodology reported provides generic strategies that can be exploited for small-scale sensors in single or multiplex formats
The design of microfluidic affinity chromatography systems for the separation of bioanalytes
No full textThe analytical (numerical) design of planar microfluidic affinity chromatography devices, which consist of multiple separation lanes and multiple, different surface-immobilised receptor patterns in each lane, is described. The model is based on the analytical solution of the transport-reaction equations in microfluidic systems of low Gratz number and for injection of small analyte plugs. The results reveal a simple approach for the design of microfluidic affinity chromatography devices tailored to the separation of bioanalytes, where receptors with high binding affinity are available. These devices have been designed for bioanalytical applications in mind, most notably for the proteomics field; the results are illustrated with an example using β-Amyloid binding peptides
Design of novel microfluidic concentration gradient generators suitable for linear and exponential concentration ranges
No full textA novel microfluidic concentration gradient generator is designed where secondary flow, induced via a surface groove, is used to yield a concentration gradient across the output of the microfluidic device. The concentration gradient generator design consists of a single microfluidic channel with two inputs and a single obliquely angled surface groove within the base of the channel to induce the secondary flow and create the concentration gradient. The design allows a concentration gradient to be chosen, either linear or exponential, at the exit of the microfluidic channel with the shape and dimensions of the surface groove within the channel obtained by numerical optimisation. The designed device has a small footprint, suitable for integration within lab-on-a-chip structures for the delivery of a series of an agent to either (i) a single channel and with a concentration gradient or to (ii) a series of reactors with concentrations across a defined range, for bioscience or pharmaceutical screening applications or for chemical reactions
Residual stress generation and necrosis formation in multi-cell tumour spheroids
No full textWe consider how cell proliferation and death generate residual stresses within a multi-cell tumour spheroid (MCTS). Previous work by Jones and co-workers [8] has shown that isotropic growth in a purely elastic MCTS produces growth induced stresses which eventually become unbounded, and hence are physically unrealistic. Since viscoelastic materials show stress relaxation under a fixed deformation we consider the effect of the addition of a small amount of viscosity to the elastic system by examining formation of equilibrium stress profiles within a Maxwell type viscoelastic MCTS. A model of necrosis formation based upon that proposed by Please and co-workers (see [16] [17] [18]) is then presented in which necrosis forms under conditions of adverse mechanical stress rather than in regions of extreme chemical stress as is usually assumed. The influence of rheology on necrosis formation is then investigated, and it is shown that the excessive stress generated in the purely elastic tumour can be relieved either by the addition of some viscosity to the system or by accounting for an inner necrotic interface with an appropriate stress boundary condition
Heterogeneous proliferation within engineered cartilaginous tissue: the role of oxygen tension
No full textThis article investigates heterogeneous proliferation within a seeded three-dimensional scaffold structure with the purpose of improving protocols for engineered tissue growth. A simple mathematical model is developed to examine the very strong interaction between evolving oxygen profiles and cell distributions within cartilaginous constructs. A comparison between predictions based on the model and experimental evidence is given for both spatial and temporal evolution of the oxygen tension and cell number density, showing that behaviour for the first 14 days can be explained well by the mathematical model. The dependency of the cellular proliferation rate on the oxygen tension is examined and shown to be similar in size to previous work but linear in form. The results show that cell-scaffold constructs that rely solely on diffusion for their supply of nutrients will inevitably produce proliferation-dominated regions near the outer edge of the scaffold in situations when the cell number density and oxygen consumption rate exceed a critical level. Possible strategies for reducing such non-uniform proliferation, including the conventional methods of enhancing oxygen transport, are outlined based on the model predictions
Physical modelling of the slow voltage relaxation phenomenon in lithium-ion batteries
Full text linkIn the lithium-ion battery literature, discharges followed by a relaxation to
equilibrium are frequently used to validate models and their parametrizations.
Good agreement with experiment during discharge is easily attained with a
pseudo-two-dimensional model such as the Doyle-Fuller-Newman (DFN) model. The
relaxation portion, however, is typically not well-reproduced, with the
relaxation in experiments occurring much more slowly than in models. In this
study, using a model that includes a size distribution of the active material
particles, we give a physical explanation for the slow relaxation phenomenon.
This model, the Many-Particle-DFN (MP-DFN), is compared against discharge and
relaxation data from the literature, and optimal fits of the size distribution
parameters (mean and variance), as well as solid-state diffusivities, are found
using numerical optimization. The voltage after relaxation is captured by
careful choice of the current cut-off time, allowing a single set of physical
parameters to be used for all C-rates, in contrast to previous studies. We find
that the MP-DFN can accurately reproduce the slow relaxation, across a range of
C-rates, whereas the DFN cannot. Size distributions allow for greater internal
heterogeneities, giving a natural origin of slower relaxation timescales that
may be relevant in other, as yet explained, battery behavior
Stochasticity and the molecular mechanisms of induced pluripotency
Full text linkThe generation of induced pluripotent stem cells from adult somatic cells by ectopic expression of key transcription factors holds significant medical promise. However, current techniques for inducing pluripotency rely on viral infection and are therefore not, at present, viable within a clinical setting. Thus, there is now a need to better understand the molecular basis of stem cell pluripotency and lineage specification in order to investigate alternative methods to induce pluripotency for clinical application. However, the complexity of the underlying molecular circuitry makes this a conceptually difficult task. In order to address these issues, we considered a computational model of transcriptional control of cell fate specification. The model comprises two mutually interacting sub-circuits: a central pluripotency circuit consisting of interactions between stem-cell specific transcription factors OCT4, SOX2 and NANOG coupled to a differentiation circuit consisting of interactions between lineage-specifying master genes.The molecular switches which arise from feedback loops within these circuits give rise to a well-defined sequence of successive gene restrictions corresponding to a controlled differentiation cascade in response to environmental stimuli. Furthermore, we found that this differentiation cascade is strongly unidirectional: once silenced, core transcription factors cannot easily be reactivated. In the context of induced pluripotency, this indicates that differentiated cells are robustly resistant to reprogramming to a more primitive state. However, our model suggests that under certain circumstances, amplification of low-level fluctuations in transcriptional status (transcriptional "noise") may be sufficient to trigger reactivation of the core pluripotency switch and reprogramming to a pluripotent state. This interpretation offers an explanation of a number of experimental observations concerning the molecular mechanisms of cellular reprogramming by defined factors and suggests a role for stochasticity in reprogramming of somatic cells to pluripotency<br/
A continuum model for the development of tissue-engineered cartilage around a chondrocyte
No full textThe limited ability of cartilage to repair when damaged has led to the investigation of tissue engineering as a method for reconstructing cartilage. We propose a continuum multispecies model for the development of cartilage around a single chondrocyte. As in healthy cartilage, the model predicts a balance between synthesis, transport, binding and decay of matrix components. Two mechanisms are investigated for the transport of soluble matrix components: diffusion and advection, caused by displacement of the scaffold medium. Numerical results indicate that a parameter defined by the ratio of the flux of soluble components out of the chondrocyte and its diffusive flux determines which of these mechanisms is dominant. We investigate the diffusion-dominated and advection-dominated limiting cases using perturbation analysis. Using parameter values from the literature, our modelling results suggest that both diffusion and advection are significant mechanisms in developing cartilage. Moreover, in this parameter regime, results are particularly sensitive to parameter values. These two observations could explain differences observed experimentally between various scaffold media. Modelling results are also used to predict the minimum chondrocyte seeding density required to produce functional cartilage. <br/
Experimental characterization and computational modelling of two-dimensional cell spreading for skeletal regeneration
No full textLimited cell ingrowth is a major problem for tissue engineering and the clinical application of porous biomaterials as bone substitutes. As a first step, migration and proliferation of an interacting cell population can be studied in two-dimensional culture. Mathematical modelling is essential to generalize the results of these experiments and to derive the intrinsic parameters that can be used for predictions. However, a more thorough evaluation of theoretical models is hampered by limited experimental observations. In this study, experiments and image analysis methods were developed to provide a detailed spatial and temporal picture of how cell distributions evolve. These methods were used to quantify the migration and proliferation of skeletal cell types including MG63 and human bone marrow stromal cells (HBMSCs). The high level of detail with which the cell distributions were mapped enabled a precise assessment of the correspondence between experimental results and theoretical model predictions. This analysis revealed that the standard Fisher equation is appropriate for describing the migration behaviour of the HBMSC population, while for the MG63 cells a sharp front model is more appropriate. In combination with experiments, this type of mathematical model will prove useful in predicting cell ingrowth and improving strategies and control of skeletal tissue regeneration
Asymptotic solution of a model for bilayer organic diodes and solar cells
Full text linkOrganic diodes and solar cells are constructed by placing together two organic semiconducting materials with dissimilar electron affinities and ionization potentials. The electrical behavior of such devices has been successfully modeled numerically using conventional drift diffusion together with recombination (which is usually assumed to be bimolecular) and thermal generation. Here a particular model is considered and the dark current-voltage curve and the spatial structure of the solution across the device is extracted analytically using asymptotic methods. We concentrate on the case of Shockley-Read-Hall recombination but note the extension to other recombination mechanisms. We find that there are three regimes of behavior, dependent on the total current. For small currents-i.e., at reverse bias or moderate forward bias-the structure of the solution is independent of the total current. For large currents-i.e., at strong forward bias-the current varies linearly with the voltage and is primarily controlled by drift of charges in the organic layers. There is then a narrow range of currents where the behavior undergoes a transition between the two regimes. The magnitude of the parameter that quantifies the interfacial recombination rate is critical in determining where the transition occurs. The extension of the theory to organic solar cells generating current under illumination is discussed as is the analogous current-voltage curves derived where the photo current is small. Finally, by comparing the analytic results to real experimental data, we show how the model parameters can be extracted from the shape of current-voltage curves measured in the dark. © 2012 Society for Industrial and Applied Mathematics
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