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Small-angle scattering (SAS) experiments are a powerful method for studying self-assembly phenomena in nanoscopic materials because of the sensitivity of the technique to structures formed by interactions on the nanoscale. Numerous out-of-the-box options exist for analysing structures measured by SAS but many of these are underpinned by assumptions about the underlying interactions that are not always relevant for a given system. Here, a numerical algorithm based on reverse Monte Carlo simulations is described to model the intensity observed on a SAS detector as a function of the scattering vector. The model simulates a two-dimensional detector image, accounting for magnetic scattering, instrument resolution, particle polydispersity and particle collisions, while making no further assumptions about the underlying particle interactions. By simulating a two-dimensional image that can be potentially anisotropic, the algorithm is particularly useful for studying systems driven by anisotropic interactions. The final output of the algorithm is a relative particle distribution, allowing visualization of particle structures that form over long-range length scales ( i.e. several hundred nanometres), along with an orientational distribution of magnetic moments. The effectiveness of the algorithm is shown by modelling a SAS experimental data set studying finite-length chains consisting of magnetic nanoparticles, which assembled in the presence of a strong magnetic field due to dipole interactions., (© Lester C. Barnsley et al. 2022.)

Lipid structural diversity strongly affects biomembrane chemico-physical and structural properties in addition to membrane-associated events. At high concentrations, cholesterol increases membrane order and rigidity, while polyunsaturated lipids are reported to increase disorder and flexibility. How these different tendencies balance in composite bilayers is still controversial. In this study, electron paramagnetic resonance spectroscopy, small angle neutron scattering, and neutron reflectivity were used to investigate the structural properties of cholesterol-containing lipid bilayers in the fluid state with increasing amounts of polyunsaturated omega-3 lipids. Either the hybrid 1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine or the symmetric 1,2-docosahexaenoyl-sn-glycero-3-phosphocholine were added to the mixture of the naturally abundant 1-palmitoyl-2-oleyl-sn-glycero-3-phosphocholine and cholesterol. Our results indicate that the hybrid and the symmetric omega-3 phospholipids affect the microscopic organization of lipid bilayers differently. Cholesterol does not segregate from polyunsaturated phospholipids and, through interactions with them, is able to suppress the formation of non-lamellar structures induced by the symmetric polyunsaturated lipid. However, this order/disorder balance leads to a bilayer whose structural organization cannot be ascribed to either a liquid ordered or to a canonical liquid disordered phase, in that it displays a very loose packing of the intermediate segments of lipid chains.

The introduction of "water-in-salt" electrolyte (WiSE) concept opens a new horizon to aqueous electrochemistry that is benefited from the formation of a solid-electrolyte interphase (SEI). However, such SEI still faces multiple challenges, including dissolution, mechanical damaging, and incessant reforming, which result in poor cycling stability. Here, we report a polymeric additive, polyacrylamide (PAM) that effectively stabilizes the interphase in WiSE. With the addition of 5 molar % PAM to 21 mol kg -1 LiTFSI electrolyte, a LiMn 2 O 4 ∥L-TiO 2 full cell exhibits enhanced cycling stability with 86 % capacity retention after 100 cycles at 1 C. The formation mechanism and evolution of PAM-assisted SEI was investigated using operando small angle neutron scattering and density functional theory (DFT) calculations, which reveal that PAM minimizes the presence of free water molecules at the anode/electrolyte interface, accelerates the TFSI - anion decomposition, and densifies the SEI., (© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Polyunsaturated omega-3 fatty acid docosahexaenoic acid (DHA) is found in very high concentrations in a few peculiar tissues, suggesting that it must have a specialized role. DHA was proposed to affect the function of the cell membrane and related proteins through an indirect mechanism of action, based on the DHA-phospholipid effects on the lipid bilayer structure. In this respect, most studies have focused on its influence on lipid-rafts, somehow neglecting the analysis of effects on liquid disordered phases that constitute most of the cell membranes, by reporting in these cases only a general fluidifying effect. In this study, by combining neutron reflectivity, cryo-transmission electron microscopy, small angle neutron scattering, dynamic light scattering and electron paramagnetic resonance spectroscopy, we characterize liquid disordered bilayers formed by the naturally abundant 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine and different contents of a di-DHA glycero-phosphocholine, 22:6-22:6PC, from both a molecular/microscopic and supramolecular/mesoscopic viewpoint. We show that, below a threshold concentration of about 40% molar percent, incorporation of 22:6-22:6PC in the membrane increases the lipid dynamics slightly but sufficiently to promote the membrane deformation and increase of multilamellarity. Notably, beyond this threshold, 22:6-22:6PC disfavours the formation of lamellar phases, leading to a phase separation consisting mostly of small spherical particles that coexist with a minority portion of a lipid blob with water-filled cavities. Concurrently, from a molecular viewpoint, the polyunsaturated acyl chains tend to fold and expose the termini to the aqueous medium. We propose that this peculiar tendency is a key feature of the DHA-phospholipids making them able to modulate the local morphology of biomembranes.

Recent pre-clinical studies have demonstrated the potential of combining chemotherapy and sonodynamic therapy for the treatment of pancreatic cancer. Oxygen-loaded magnetic microbubbles have been explored as a targeted delivery vehicle for this application. Despite preliminary positive results, a previous study identified a significant practical challenge regarding the co-alignment of the magnetic and ultrasound fields. The aim of this study was to determine whether this challenge could be addressed through the use of a magnetic-acoustic device (MAD) combining a magnetic array and ultrasound transducer in a single unit, to simultaneously concentrate and activate the microbubbles at the target site. in vitro experiments were performed in tissue phantoms and followed by in vivo treatment of xenograft pancreatic cancer (BxPC-3) tumours in a murine model. In vitro, a 1.4-fold (p < .01) increase in the deposition of a model therapeutic payload within the phantom was achieved using the MAD compared to separate magnetic and ultrasound devices. In vivo, tumours treated with the MAD had a 9% smaller mean volume 8 days after treatment, while tumours treated with separate devices or microbubbles alone were respectively 45% and 112% larger. This substantial and sustained decrease in tumour volume suggests that the proposed drug delivery approach has the potential to be an effective neoadjuvant therapy for pancreatic cancer patients., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

The self-assembly of the two anomeric forms of n -hexadecyl-d-maltopyranoside (denoted α-C 16 G 2 and β-C 16 G 2 ) has been studied in dilute aqueous solution by means of surface tension measurements, scattering methods (dynamic light scattering, static light scattering, and small-angle X-ray and neutron scattering), and cryo-transmission electron microscopy at different surfactant concentrations and temperatures. Surface tension measurements demonstrate differences in the surfactant adsorption at the air-water interface, where α-C 16 G 2 shows a lower CMC than β-C 16 G 2 . Similarly, micelle morphology was found to profoundly depend on anomerism. β-C 16 G 2 preferentially forms very elongated micelles with large persistence lengths, whereas α-C 16 G 2 assembles into smaller micelles for which the structure varies with concentration and temperature. The differences between the two surfactant anomers in terms of self-assembly can be attributed to the interaction between neighboring headgroups. Specifically, β-C 16 G 2 allows for a closer packing in the palisade layer, hence reducing the micelle curvature and promoting the formation of more elongated micelles. Strong intermolecular headgroup interactions may also account for the observed rigidity of the micelles.

Smart, fully orthogonal switching was realized in a highly biocompatible diblock copolymer system with variable trigger-induced aqueous self-assembly. The polymers are composed of nonionic and zwitterionic blocks featuring lower and upper critical solution temperatures (LCSTs and UCSTs). In the system investigated, diblock copolymers from poly( N-isopropyl methacrylamide) (PNIPMAM) and a poly(sulfobetaine methacrylamide), systematic variation of the molar mass of the latter block allowed for shifting the UCST of the latter above the LCST of the PNIPMAM block in a salt-free condition. Thus, successive thermal switching results in "schizophrenic" micellization, in which the roles of the hydrophobic core block and the hydrophilic shell block are interchanged depending on the temperature. Furthermore, by virtue of the strong electrolyte-sensitivity of the zwitterionic polysulfobetaine block, we succeeded to shift its UCST below the LCST of the PNIPMAM block by adding small amounts of an electrolyte, thus inverting the pathway of switching. This superimposed orthogonal switching by electrolyte addition enabled us to control the switching scenarios between the two types of micelles (i) via an insoluble state, if the LCST-type cloud point is below the UCST-type cloud point, which is the case at low salt concentrations or (ii) via a molecularly dissolved state, if the LCST-type cloud point is above the UCST-type cloud point, which is the case at high salt concentrations. Systematic variation of the block lengths allowed for verifying the anticipated behavior and identifying the molecular architecture needed. The versatile and tunable self-assembly offers manifold opportunities, for example, for smart emulsifiers or for sophisticated carrier systems.

Microbubble-enhanced sonothrombolysis is a promising approach to increasing the tolerability and efficacy of current pharmacological treatments for ischemic stroke. Maintaining therapeutic concentrations of microbubbles and drugs at the clot site, however, poses a challenge. The objective of this study was to investigate the effect of magnetic microbubble targeting upon clot lysis rates in vitro. Retracted whole porcine blood clots were placed in a flow phantom of a partially occluded middle cerebral artery. The clots were treated with a combination of tissue plasminogen activator (0.75 µg/mL), magnetic microbubbles (∼10 7 microbubbles/mL) and ultrasound (0.5 MHz, 630-kPa peak rarefactional pressure, 0.2-Hz pulse repetition frequency, 2% duty cycle). Magnetic targeting was achieved using a single permanent magnet (0.08-0.38 T and 12-140 T/m in the region of the clot). The change in clot diameter was measured optically over the course of the experiment. Magnetic targeting produced a threefold average increase in lysis rates, and linear correlation was observed between lysis rate and total energy of acoustic emissions., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

We report the design and characterization of a lateral and vertical hydrodynamic focusing feature for whole cell detection on a miniaturized flow cytometer. The developed system, based on magnetic sensing, incorporates spin valve sensors on the bottom of the microfluidic channels that detect cells labeled with magnetic beads. An adaptable 3D hydrodynamic focusing system was developed that pushes labeled cells towards the bottom of the microchannel, closer to the sensors, allowing increased signal amplitude for cells labeled with magnetic beads and enhanced discrimination of labeled cells. Fluorescence microscopy indicates that the lateral and vertical hydrodynamic focusing effect was adequately implemented, consistent with simulation predictions. The sensitivity of the system to detect labeled cells was improved by at least two-fold. By estimating the coverage of magnetic beads on cells, the signal from labeled cells could be predicted using a mathematical model, which also demonstrated the sensitivity of the signal to the height of the cells relative to the sensor. The system is versatile allowing interchangeable flow rates for cells with different diameters.

Magnetically responsive microbubbles (MagMBs), consisting of an oxygen gas core and a phospholipid coating functionalised with Rose Bengal (RB) and/or 5-fluorouracil (5-FU), were assessed as a delivery vehicle for the targeted treatment of pancreatic cancer using combined antimetabolite and sonodynamic therapy (SDT). MagMBs delivering the combined 5-FU/SDT treatment produced a reduction in cell viability of over 50% when tested against a panel of four pancreatic cancer cell lines in vitro. Intravenous administration of the MagMBs to mice bearing orthotopic human xenograft BxPC-3 tumours yielded a 48.3% reduction in tumour volume relative to an untreated control group (p<0.05) when the tumour was exposed to both external magnetic and ultrasound fields during administration of the MagMBs. In contrast, application of an external ultrasound field alone resulted in a 27% reduction in tumour volume. In addition, activated caspase and BAX protein levels were both observed to be significantly elevated in tumours harvested from animals treated with the MagMBs in the presence of magnetic and ultrasonic fields when compared to expression of those proteins in tumours from either the control or ultrasound field only groups (p<0.05). These results suggest MagMBs have considerable potential as a platform to enable the targeted delivery of combined sonodynamic/antimetabolite therapy in pancreatic cancer., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Ultrasound and microbubbles have been shown to accelerate the breakdown of blood clots both in vitro and in vivo. Clinical translation of this technology is still limited, however, in part by inefficient microbubble delivery to the thrombus. This study examines the obstacles to delivery posed by fluid dynamic conditions in occluded vasculature and investigates whether magnetic targeting can improve microbubble delivery. A 2D computational fluid dynamic model of a fully occluded Y-shaped microarterial bifurcation was developed to determine: (i) the fluid dynamic field in the vessel with inlet velocities from 1-100 mm s -1 (corresponding to Reynolds numbers 0.25-25); (ii) the transport dynamics of fibrinolytic drugs; and (iii) the flow behavior of microbubbles with diameters in the clinically-relevant range (0.6-5 µm). In vitro experiments were carried out in a custom-built microfluidic device. The flow field was characterized using tracer particles, and fibrinolytic drug transport was assessed using fluorescence microscopy. Lipid-shelled magnetic microbubbles were fluorescently labelled to determine their spatial distribution within the microvascular model. In both the simulations and experiments, the formation of laminar vortices and an abrupt reduction of fluid velocity were observed in the occluded branch of the bifurcation, severely limiting drug transport towards the occlusion. In the absence of a magnetic field, no microbubbles reached the occlusion, remaining trapped in the first vortex, within 350 µm from the bifurcation center. The number of microbubbles trapped within the vortex decreased as the inlet velocity increased, but was independent of microbubble size. Application of a magnetic field (magnetic flux density of 76 mT, magnetic flux density gradient of 10.90 T m -1 at the centre of the bifurcation) enabled delivery of microbubbles to the occlusion and the number of microbubbles delivered increased with bubble size and with decreasing inlet velocity.

The aim of this study was to characterize the behaviour of superparamagnetic particles in magnetic drug targeting (MDT) schemes. A 3-dimensional mathematical model was developed, based on the analytical derivation of the trajectory of a magnetized particle suspended inside a fluid channel carrying laminar flow and in the vicinity of an external source of magnetic force. Semi-analytical expressions to quantify the proportion of captured particles, and their relative accumulation (concentration) as a function of distance along the wall of the channel were also derived. These were expressed in terms of a non-dimensional ratio of the relevant physical and physiological parameters corresponding to a given MDT protocol. The ability of the analytical model to assess magnetic targeting schemes was tested against numerical simulations of particle trajectories. The semi-analytical expressions were found to provide good first-order approximations for the performance of MDT systems in which the magnetic force is relatively constant over a large spatial range. The numerical model was then used to test the suitability of a range of different designs of permanent magnet assemblies for MDT. The results indicated that magnetic arrays that emit a strong magnetic force that varies rapidly over a confined spatial range are the most suitable for concentrating magnetic particles in a localized region. By comparison, commonly used magnet geometries such as button magnets and linear Halbach arrays result in distributions of accumulated particles that are less efficient for delivery. The trajectories predicted by the numerical model were verified experimentally by acoustically focusing magnetic microbeads flowing in a glass capillary channel, and optically tracking their path past a high field gradient Halbach array.

A key challenge in the development of magnetic drug targeting (MDT) as a clinically relevant technique is designing systems that can apply sufficient magnetic force to actuate magnetic drug carriers at useful tissue depths. In this study an optimisation routine was developed to generate designs of Halbach arrays consisting of multiple layers of high grade, cubic, permanent magnet elements, configured to deliver the maximum pull or push force at a position of interest between 5 and 50 mm from the array, resulting in arrays capable of delivering useful magnetic forces to depths past 20 mm. The optimisation routine utilises a numerical model of the magnetic field and force generated by an arbitrary configuration of magnetic elements. Simulated field and force profiles of optimised arrays were evaluated, also taking into account the forces required for assembling the array in practice. The resultant selection for the array, consisting of two layers, was then constructed and characterised to verify the simulations. Finally the array was utilised in a set of in vitro experiments to demonstrate its capacity to separate and retain microbubbles loaded with magnetic nanoparticles against a constant flow. The optimised designs are presented as light-weight, inexpensive options for applying high-gradient, external magnetic fields in MDT applications.

The magnetic hysteresis loops of an aged Cu(81.2)Mn(18.8) alloy sample exhibit significant asymmetric reversal at low temperatures, with high sensitivity to the cooling field. Much of the observed behaviour was explained by considering an ensemble of coherent, ferromagnetically aligned clusters interacting with a randomized spin glass component. A modified Stoner-Wohlfarth model was successfully applied to the data using Monte Carlo simulations, in order to gain insight into the dependence of the cluster shape anisotropy and exchange anisotropy on the cooling field. This model suggested that ferromagnetic clusters grow as the cooling field increases.