Packaging biological cargoes in mesoporous materials: Opportunities for drug delivery

Introduction: Confinement of biomolecules in structured nanoporous materials offers several desirable features ranging from chemical and thermal stability, to resistance to degradation from the external environment. A new generation of mesoporous materials presents exciting new possibilities for the formulation and controlled release of biological agents. Such materials address niche applications in enteral and parenteral delivery of biologics, such as peptides, polypeptides, enzymes and proteins for use as therapeutics, imaging agents, biosensors, and adjuvants.Areas covered: Mesoporous silica Santa Barbara Amorphous-15 (SBA-15), with its unique, tunable pore diameter, and easily functionalized surface, provides a representative example of this new generation of materials. Here, we review recent advances in the design and synthesis of nanostructured mesoporous materials, focusing on SBA-15, and highlight opportunities for the delivery of biological agents to various organ and tissue compartments.Expert opinion: The SBA-15 platform provides a delivery carrier that is inherently separated from the active biologic due to distinct intra and extra-particle environments. This permits the SBA-15 platform to not require direct modification of the active biological therapeutic. Additionally, this makes the platform universal and allows for its application independent of the desired methods of discovery and development. The SBA-15 platform also directly addresses issues of targeted delivery and controlled release, although future challenges in the implementation of this platform reside in particle design, biocompatibility, and the tunability of the internal and external material properties. Examples illustrating the flexibility in the application of the SBA-15 platform are also discussed

Transition from Knudsen to molecular diffusion in activity of absorbing irregular interfaces

We investigate through molecular dynamics the transition from Knudsen to molecular diffusion transport towards 2d absorbing interfaces with irregular geometry. Our results indicate that the length of the active zone decreases continuously with density from the Knudsen to the molecular diffusion regime. In the limit where molecular diffusion dominates, we find that this length approaches a constant value of the order of the system size, in agreement with theoretical predictions for Laplacian transport in irregular geometries. Finally, we show that all these features can be qualitatively described in terms of a simple random-walk model of the diffusion process.Comment: 4 pages, 4 figure

Steady-State Properties of Single-File Systems with Conversion

We have used Monte-Carlo methods and analytical techniques to investigate the influence of the characteristic parameters, such as pipe length, diffusion, adsorption, desorption and reaction rate constants on the steady-state properties of Single-File Systems with a reaction. We looked at cases when all the sites are reactive and when only some of them are reactive. Comparisons between Mean-Field predictions and Monte-Carlo simulations for the occupancy profiles and reactivity are made. Substantial differences between Mean-Field and the simulations are found when rates of diffusion are high. Mean-Field results only include Single-File behavior by changing the diffusion rate constant, but it effectively allows passing of particles. Reactivity converges to a limit value if more reactive sites are added: sites in the middle of the system have little or no effect on the kinetics. Occupancy profiles show approximately exponential behavior from the ends to the middle of the system.Comment: 15 pages, 20 figure

Optimizing the architecture of lung-inspired fuel cells

A finite-element model of a polymer electrolyte membrane fuel cell (PEMFC) with fractal branching, lung-inspired flow-field is presented. The effect of the number of branching generations N on the thickness of the gas diffusion layer (GDL) and fuel cell performance is determined. Introduction of a fractal flow-field to homogenize reactant concentration at the flow-field | GDL interface allows for the use of thinner GDLs. The model is coupled with an optimized cathode catalyst layer microstructure with respect to platinum utilization and power density, revealing that the 2020 DoE target of ~8 kW/gPt is met at N = 4 generations, and a platinum utilization of ~36 kW/gPt is achieved at N = 6 generations. In terms of the overall fuel cell stack architecture, our results indicate that either the platinum loading or the number of cells in the stack can be reduced by ~75%, the latter option of which, when combined with a 100 µm GDL, can lead to >80% increase in the volumetric power density of the fuel cell stack

Transient behavior in Single-File Systems

We have used Monte-Carlo methods and analytical techniques to investigate the influence of the characteristics, such as pipe length, diffusion, adsorption, desorption and reaction rates on the transient properties of Single-File Systems. The transient or the relaxation regime is the period in which the system is evolving to equilibrium. We have studied the system when all the sites are reactive and when only some of them are reactive. Comparisons between Mean-Field predictions, Cluster Approximation predictions, and Monte Carlo simulations for the relaxation time of the system are shown. We outline the cases where Mean-Field analysis gives good results compared to Dynamic Monte-Carlo results. For some specific cases we can analytically derive the relaxation time. Occupancy profiles for different distribution of the sites both for Mean-Field and simulations are compared. Different results for slow and fast reaction systems and different distribution of reactive sites are discussed.Comment: 18 pages, 19 figure

A lung-inspired approach to scalable and robust fuel cell design

A lung-inspired approach is employed to overcome reactant homogeneity issues in polymer electrolyte fuel cells. The fractal geometry of the lung is used as the model to design flow-fields of different branching generations, resulting in uniform reactant distribution across the electrodes and minimum entropy production of the whole system. 3D printed, lung-inspired flow field based PEFCs with N = 4 generations outperform the conventional serpentine flow field designs at 50% and 75% RH, exhibiting a 20% and 30% increase in performance (at current densities higher than 0.8 A cm2) and maximum power density, respectively. In terms of pressure drop, fractal flow-fields with N = 3 and 4 generations demonstrate 75% and 50% lower values than conventional serpentine flow-field design for all RH tested, reducing the power requirements for pressurization and recirculation of the reactants. The positive effect of uniform reactant distribution is pronounced under extended current-hold measurements, where lung-inspired flow field based PEFCs with N = 4 generations exhibit the lowest voltage decay (B5 mV h1). The enhanced fuel cell performance and low pressure drop values of fractal flow field design are preserved at large scale (25 cm2), in which the excessive pressure drop of a large-scale serpentine flow field renders its use prohibitive

Hydration state diagnosis in fractal flow-field based polymer electrolyte membrane fuel cells using acoustic emission analysis

Techniques for evaluating water management are critical to diagnose the performance of polymer electrolyte membrane fuel cells (PEMFCs). Acoustic emission as a function of polarisation (AEfP) has been recently introduced as a non-invasive, non-destructive method to analyse the water generation and removal inside a PEMFC during polarisation. AEfP was shown to provide unique insight into water management within a conventional PEMFC and correlating it to cell performance. Here, AEfP is used to characterise the performance of fractal PEMFCs by evaluating the hydration conditions inside them. This is achieved by probing the water dynamics inside two different fractal flow-field based PEMFCs, namely 1-way and 2-way fractal PEMFCs, and measuring the corresponding acoustic activity generated from them. AEfP is performed on the fractal PEMFCs under relatively humid (70% RH) and fully humidified (100% RH) reactant relative humidity (RH) conditions. Flooding in the 2-way fractal PEMFC, as opposed to the 1-way fractal PEMFC, is demonstrated under different operating conditions by the relatively higher acoustic activity it generates. Corroborating evidence of flooding in the 2-way fractal flow-field under different conditions is provided by its polarisation curves, impedance tests and galvanostatic (current hold) measurements

Code renewability for native software protection

Software protection aims at safeguarding assets embedded in software by preventing and delaying reverse engineering and tampering attacks. This article presents an architecture and supporting tool flow to renew parts of native applications dynamically. Renewed and diversified code and data belonging to either the original application or to linked-in protections are delivered from a secure server to a client on demand. This results in frequent changes to the software components when they are under attack, thus making attacks harder. By supporting various forms of diversification and renewability, novel protection combinations become available and existing combinations become stronger. The prototype implementation is evaluated on several industrial use cases