Correction: Smartphone-read phage lateral flow assay for point-of-care detection of infection.

Correction for 'Smartphone-read phage lateral flow assay for point-of-care detection of infection' by Maede Chabi, et al., Analyst, 2023, 148, 839-848, https://doi.org/10.1039/D2AN01499H.

A minimal colloid model of solution crystallization nucleates crystals classically.

A fundamental assumption of the classical theories of crystal nucleation is that the individual molecules from the "old" phase associate to an emerging nucleus individually and sequentially. Numerous recent studies of crystal nucleation in solution have revealed nonclassical pathways, whereby crystal nuclei are hosted and fed by amorphous clusters pre-formed in the solution. A sizable knowledge gap has persisted, however, in the definition of the molecular-level parameters that direct a solute towards classical or nonclassical nucleation. Here we construct a suspension of colloid particles of hydrodynamic diameter 1.1 µm and monitor their individual motions towards a quasi-two-dimensional crystal by scanning confocal microscopy. We combine electrostatic repulsion and polymer-induced attraction to obtain a simple isotropic pair interaction potential with a single attractive minimum of tunable depth between 1.2kBT and 2.7kBT. We find that even the smallest aggregates that form in this system structure as hexagonal two-dimensional crystals and grow and maturate by the association and exchange of single particles from the solution, signature behaviors during classical nucleation. The particles in the suspension equilibrate with those in the clusters and the volume fractions of suspensions at equilibrium correspond to straightforward thermodynamic predictions based on depth of the interparticle attraction. These results demonstrate that classical nucleation is selected by particles interacting with a minimal potential and present a benchmark for future modifications of the molecular interactions that may induce nonclassical nucleation.

Particle dispersion through porous media with heterogeneous attractions.

Porous media used in many practical applications contain natural spatial variations in composition and surface charge that lead to heterogeneous physicochemical attractions between the media and transported particles. We performed Stokesian dynamics (SD) simulations to examine the effects of heterogeneous attractions on quiescent diffusion and hydrodynamic dispersion of particles within geometrically ordered arrays of nanoposts. We find that transport under quiescent conditions occurs by two mechanisms, diffusion through the void space and intermittent hopping between the attractive wells of different nanoposts. As the attraction heterogeneity increases, the latter mechanism becomes dominant, resulting in an increase in the particle trajectory tortuosity, deviations from Gaussian behavior in the particle displacement distributions, and a decrease in the long-time particle diffusivity. Similarly, under flow conditions corresponding to low Péclet number (Pe), increased attraction heterogeneity leads to transient localization near the nanoposts, resulting in a broadening of the particle distribution and enhanced longitudinal dispersion in the direction of flow. At high Pe where advection strongly dominates, however, the longitudinal dispersion coefficient is insensitive to attraction heterogeneity and exhibits Taylor-Aris dispersion behavior. Our findings provide insight into how heterogeneous interactions may influence particle transport in complex 3-D porous media.

Confined Dynamics in Spherical Polymer Brushes.

We investigate the dynamics of polymers grafted to spherical nanoparticles in solution using hybrid molecular dynamics simulations with a coarse-grained solvent modeled via the multiparticle collision dynamics algorithm. The mean-square displacements of monomers near the surface of the nanoparticle exhibit a plateau on intermediate time scales, indicating confined dynamics reminiscent of those reported in neutron spin-echo experiments. The confined dynamics vanish beyond a specific radial distance from the nanoparticle surface that depends on the polymer grafting density. We show that this dynamical confinement transition follows theoretical predictions for the critical distance associated with the structural transition from confined to semidilute brush regimes. These findings suggest the existence of a hitherto unreported dynamic length scale connected with theoretically predicted static fluctuations in spherical polymer brushes and provide new insights into recent experimental observations.

Imaging Heterogeneous 3D Dynamics of Individual Solutes in a Polyelectrolyte Brush.

Understanding molecular transport in polyelectrolyte brushes (PEBs) is crucial for applications such as separations, drug delivery, anti-fouling, and biosensors, where structural features of the polymer control intermolecular interactions. The complex structure and local heterogeneity of PEBs, while theoretically predicted, are not easily accessed with conventional experimental methods. In this work, we use 3D single-molecule tracking to understand transport behavior within a cationic poly(2-(N,N-dimethylamino)ethyl acrylate) (PDMAEA) brush using an anionic dye, Alexa Fluor 546, as the probe. The analysis is done by a parallelized, unbiased 3D tracking algorithm. Our results explicitly demonstrate that spatial heterogeneity within the brush manifests as heterogeneity of single-molecule displacements. Two distinct populations of probe motion are identified, with anticorrelated axial and lateral transport confinement, which we believe to correspond to intra- vs inter-chain probe motion.

pH response of sequence-controlled polyampholyte brushes.

We use molecular simulation to investigate the pH response of sequence-controlled polyampholyte brushes (PABs) with polymer chains consisting of alternating blocks of weakly acidic and basic monomers. Changes in the ionization state, height, lateral structure, and chain conformations of PABs with pH are found to differ qualitatively from those observed for polyelectrolyte brushes. Grafting density has a relatively modest effect on PAB properties. By contrast, monomer sequence strongly affects the pH response, with the extent of the response increasing with the block size. This trend is attributed to strong electrostatic attractions between oppositely charged blocks, which lead to an increase in chain backfolding as block size increases. This behavior is consistent with that observed for polyampholytes with similar monomer sequences in solution in previous studies. Our study shows that monomer sequence can be used to tune the pH response of weak PABs to generate stimuli-responsive surfaces.

Effects of Polymer Molecular Weight on Structure and Dynamics of Colloid-Polymer Bridging Systems.

We investigate the effects of polymer molecular weight on the structure and dynamics of a model colloid-polymer bridging system using confocal microscopy. Polymer-induced bridging interactions between trifluoroethyl methacrylate-co-tert-butyl methacrylate (TtMA) copolymer particles and poly(acrylic acid) (PAA) polymers of molecular weight Mw of 130, 450, 3000, or 4000 kDa and normalized concentrations c/c* ranging from 0.05 to 2 are driven by hydrogen bonding of PAA to one of the particle stabilizers. At a constant particle volume fraction ϕ = 0.05, the particles form clusters or networks of maximal size at an intermediate polymer concentration and become more dispersed upon further addition of polymer. Increasing the polymer Mw at a fixed normalized concentration c/c* increases the cluster size: suspensions with 130 kDa polymer contain small clusters that remain diffusive, and those with 4000 kDa polymer form larger, dynamically arrested clusters. Biphasic suspensions with distinct populations of disperse and arrested particles form at low c/c*, where there is insufficient polymer to bridge all particles, or high c/c*, where some particles are sterically stabilized by the added polymer. Thus, the microstructure and dynamics in these mixtures can be tuned through the size and concentration of the bridging polymer.

Shaping the Structure and Response of Surface-Grafted Polymer Brushes via the Molecular Weight Distribution.

Breadth in the molecular weight distribution is an inherent feature of synthetic polymer systems. While in the past this was typically considered as an unavoidable consequence of polymer synthesis, multiple recent studies have shown that tailoring the molecular weight distribution can alter the properties of polymer brushes grafted to surfaces. In this Perspective, we describe recent advances in synthetic methods to control the molecular weight distribution of surface-grafted polymers and highlight studies that reveal how shaping this distribution can generate novel or enhanced functionality in these materials.

Gelation and Re-entrance in Mixtures of Soft Colloids and Linear Polymers of Equal Size.

Liquid mixtures composed of colloidal particles and much smaller non-adsorbing linear homopolymers can undergo a gelation transition due to polymer-mediated depletion forces. We now show that the addition of linear polymers to suspensions of soft colloids having the same hydrodynamic size yields a liquid-to-gel-to-re-entrant liquid transition. In particular, the dynamic state diagram of 1,4-polybutadiene star-linear polymer mixtures was determined with the help of linear viscoelastic and small-angle X-ray scattering experiments. While keeping the star polymers below their nominal overlap concentration, a gel was formed upon increasing the linear polymer content. Further addition of linear chains yielded a re-entrant liquid. This unexpected behavior was rationalized by the interplay of three possible phenomena: (i) depletion interactions, driven by the size disparity between the stars and the polymer length scale which is the mesh size of its entanglement network; (ii) colloidal deswelling due to the increased osmotic pressure exerted onto the stars; and (iii) a concomitant progressive suppression of the depletion efficiency on increasing the polymer concentration due to reduced mesh size, hence a smaller range of attraction. Our results unveil an exciting new way to tailor the flow of soft colloids and highlight a largely unexplored path to engineer soft colloidal mixtures.

In colon cancer cells fascin1 regulates adherens junction remodeling.

Adherens junctions (AJs) are a defining feature of all epithelial cells. They regulate epithelial tissue architecture and integrity, and their dysregulation is a key step in tumor metastasis. AJ remodeling is crucial for cancer progression, and it plays a key role in tumor cell survival, growth, and dissemination. Few studies have examined AJ remodeling in cancer cells consequently, it remains poorly understood and unleveraged in the treatment of metastatic carcinomas. Fascin1 is an actin-bundling protein that is absent from the normal epithelium but its expression in colon cancer is linked to metastasis and increased mortality. Here, we provide the molecular mechanism of AJ remodeling in colon cancer cells and identify for the first time, fascin1's function in AJ remodeling. We show that in colon cancer cells fascin1 remodels junctional actin and actomyosin contractility which makes AJs less stable but more dynamic. By remodeling AJs fascin1 drives mechanoactivation of WNT/ß-catenin signaling and generates "collective plasticity" which influences the behavior of cells during cell migration. The impact of mechanical inputs on WNT/ß-catenin activation in cancer cells remains poorly understood. Our findings highlight the role of AJ remodeling and mechanosensitive WNT/ß-catenin signaling in the growth and dissemination of colorectal carcinomas.

Smartphone-read phage lateral flow assay for point-of-care detection of infection.

The COVID-19 pandemic has highlighted the urgent need for sensitive, affordable, and widely accessible testing at the point of care. Here we demonstrate a new, universal LFA platform technology using M13 phage conjugated with antibodies and HRP enzymes that offers high analytical sensitivity and excellent performance in a complex clinical matrix. We also report its complete integration into a sensitive chemiluminescence-based smartphone-readable lateral flow assay for the detection of SARS-CoV-2 nucleoprotein. We screened 84 anti-nucleoprotein monoclonal antibody pairs in phage LFA and identified an antibody pair that gave an LoD of 25 pg mL-1 nucleoprotein in nasal swab extract using a FluorChem gel documentation system and 100 pg mL-1 when the test was imaged and analyzed by an in-house-developed smartphone reader. The smartphone-read LFA signals for positive clinical samples tested (N = 15, with known Ct) were statistically different (p < 0.001) from signals for negative clinical samples (N = 11). The phage LFA technology combined with smartphone chemiluminescence imaging can enable the timely development of ultrasensitive, affordable point-of-care testing platforms for SARS-CoV-2 and beyond.

Long-Wavelength Fluctuations in Quasi-2D Supercooled Liquids.

We use molecular simulation to characterize the dynamics of supercooled liquids confined in quasi-2D slit geometries. Similar to bulk supercooled liquids, the confined systems exhibit subdiffusive dynamics on intermediate time scales arising from particle localization inside their neighbor cages, followed by an eventual crossover to diffusive behavior as cage rearrangement occurs. The quasi-2D confined liquids also exhibit signatures of long-wavelength fluctuations (LWFs) in the lateral directions parallel to the confining walls, reminiscent of the collective displacements observed in 2D but not 3D systems. The magnitude of the LWFs increases with the lateral dimensions of systems with the same particle volume fraction and confinement length scale, consistent with the logarithmic scaling predicted for 2D Mermin-Wagner fluctuations. The amplitude of the fluctuations is a nonmonotonic function of the confinement length scale because of a competition between caging and strengthening LWFs upon approaching the 2D limit. Our findings suggest that LWFs may play an important role in understanding the behavior of confined supercooled liquids due to their prevalence over a surprisingly broad range of particle densities and confinement length scales.

Systematic design of pulse dosing to eradicate persister bacteria.

A small fraction of infectious bacteria use persistence as a strategy to survive exposure to antibiotics. Periodic pulse dosing of antibiotics has long been considered a potentially effective strategy towards eradication of persisters. Recent studies have demonstrated through in vitro experiments that it is indeed feasible to achieve such effectiveness. However, systematic design of periodic pulse dosing regimens to treat persisters is currently lacking. Here we rigorously develop a methodology for the systematic design of optimal periodic pulse dosing strategies for rapid eradication of persisters. A key outcome of the theoretical analysis, on which the proposed methodology is based, is that bactericidal effectiveness of periodic pulse dosing depends mainly on the ratio of durations of the corresponding on and off parts of the pulse. Simple formulas for critical and optimal values of this ratio are derived. The proposed methodology is supported by computer simulations and in vitro experiments.

Fouling Resistance and Release Properties of Poly(sulfobetaine) Brushes with Varying Alkyl Chain Spacer Lengths and Molecular Weights.

We examined the effects of alkyl carbon spacer length (CSL) and molecular weight on fouling resistance and release properties of zwitterionic poly(sulfobetaine methacrylate) brushes. Using surface-initiated atom transfer radical polymerization, we synthesized two series of brushes with CSL = 3 and 4 and molecular weight from 19 to 1500 kg ·mol-1, corresponding to dry brush thickness from around 6 to 180 nm. The brush with CSL = 3 was nearly completely wet with water (independent of molecular weight), whereas the brush with CSL = 4 exhibited a strong increase in water contact angle with molecular weight. Though the two-brush series had distinct wetting properties, both series of brushes exhibited similarly great resistance against fouling by Staphylococcus epidermidis bacteria and Aspergillus niger fungi spores when submerged in water, indicating that neither molecular weight nor CSL strongly affected the antifouling behavior. We also compared the efficacy of brushes against fouling by fungi and silicon oil in air. Brushes grafted to filter paper were strongly fouled by fungi and silicon oil in air. Grafting the polymers to the filter paper, however, greatly enhanced removal of the foulant upon rinsing. The removal of fungi and silicon oil when rinsed with a salt solution was enhanced by 219 and 175%, respectively, as compared to a blank filter paper control. Thus, our results indicate that these zwitterionic brushes can promote foulant removal for dry applications in addition to their well-known fouling resistance in submerged conditions.

Aggregation and gelation in a tunable aqueous colloid-polymer bridging system.

We report a colloid-polymer model system with tunable bridging interactions for microscopic studies of structure and dynamics using confocal imaging. The interactions between trifluoroethyl methacrylate-co-tert-butyl methacrylate copolymer particles and poly(acrylic acid) (PAA) polymers were controllable via polymer concentration and pH. The strength of adsorption of PAA on the particles, driven by pH-dependent interactions with polymer brush stabilizers on the particle surfaces, was tuned via solution pH. Particle-polymer suspensions formulated at low pH, where polymers strongly adsorbed to the particles, contained clusters or weak gels at particle volume fractions of ϕ = 0.15 and ϕ = 0.40. At high pH, where the PAA only weakly adsorbed to the particle surface, particles largely remained dispersed, and the suspensions behaved as a dense fluid. The ability to visualize the suspension structure is likely to provide insight into the role of polymer-driven bridging interactions in the behavior of colloidal suspensions.

Nanoparticle transport within non-Newtonian fluid flow in porous media.

Control over dispersion of nanoparticles in polymer solutions through porous media is important for subsurface applications such as soil remediation and enhanced oil recovery. Dispersion is affected by the spatial heterogeneity of porous media, the non-Newtonian behavior of polymer solutions, and the Brownian motion of nanoparticles. Here, we use the Euler-Lagrangian method to simulate the flow of nanoparticles and inelastic non-Newtonian fluids (described by Meter model) in a range of porous media samples and injection rates. In one case, we use a fine mesh of more than 3 million mesh points to model nanoparticles transport in a sandstone sample. The results show that the velocity distribution of nanoparticles in the porous medium is non-Gaussian, which leads to the non-Fickian behavior of nanoparticles dispersion. Due to pore-space confinement, the long-time mean-square displacement of nanoparticles depends nonlinearly on time. Additionally, the gradient of shear stress in the pore space of the porous medium dictates the transport behavior of nanoparticles in the porous medium. Furthermore, the Brownian motion of nanoparticles increases the dispersion of nanoparticles along the longitudinal and transverse direction.

Nanoparticle dispersion in porous media: Effects of attractive particle-media interactions.

We investigate the effects of physicochemical attractions on the transport of finite-sized particles in three-dimensional ordered nanopost arrays using Stokesian dynamics simulations. We find that weak particle-nanopost attractions negligibly affect diffusion due to the dominance of Brownian fluctuations. Strong attractions, however, significantly hinder particle diffusion due to localization of particles around the nanoposts. Conversely, under flow, attractions significantly enhance longitudinal dispersion at low to moderate Péclet number (Pe). At high Pe, by contrast, advection becomes dominant and attractions weakly enhance dispersion. Moreover, attractions frustrate directional locking at moderate flow rates, and shift the onset of this behavior to higher Pe.

Electrostatic Repulsion Slows Relaxations of Polyelectrolytes in Semidilute Solutions.

We investigate the structure and dynamics of unentangled semidilute solutions of sodium polystyrenesulfonate (NaPSS) using small-angle neutron scattering (SANS) and neutron spin-echo (NSE) spectroscopy. The effects of electrostatic interactions and chain structure are examined as a function of ionic strength and polymer concentration, respectively. The SANS profiles exhibit a characteristic structural peak, signature of polyelectrolyte solutions, that can be fit with a combination of a semiflexible chain with excluded volume interactions form factor and a polymer reference interaction site model (PRISM) structure factor. We confirm that electrostatic interactions vary with ionic strength across solutions with similar geometries. The segmental relaxations from NSE deviate from theoretical predictions from Zimm and exhibit two scaling behaviors, with the crossover between the two regimes taking place around the characteristic structural peak. The chain dynamics are suppressed across the length scale of the correlation blob, and inversely related to the structure factor. These observations suggest that the highly correlated nature of polyelectrolytes presents an additional energy barrier that leads to de Gennes narrowing behavior.

Bacterial aggregation assisted by anionic surfactant and calcium ions.

We identify factors leading to aggregation of bacteria in the presence of a surfactant using absorbance and microscopy. Two marine bacteria, Marinobacter hydrocarbonoclasticus SP17 and Halomonas titanicae Bead 10BA, formed aggregates of a broad size distribution in synthetic sea water in the presence of an anionic surfactant, dioctyl sodium sulfosuccinate (DOSS). Both DOSS at high concentrations and calcium ions were necessary for aggregate formation, but DOSS micelles were not required for aggregation. Addition of proteinase K but not DNase1 eliminated aggregate formation over two hours. Finally, swimming motility also enhanced aggregate formation.

Nanoparticle dispersion in porous media: Effects of array geometry and flow orientation.

We investigate the effects of array geometry and flow orientation on transport of finite-sized particles in ordered arrays using Stokesian dynamics simulations. We find that quiescent diffusion is independent of array geometry over the range of volume fraction of the nanoposts examined. Longitudinal dispersion under flow depends on the direction of incident flow relative to the array lattice vectors. Taylor-Aris behavior is recovered for flow along the lattice directions, whereas a nonmonotonic dependence of the dispersion coefficient on the Péclet number is obtained for flow orientations slightly perturbed from certain lattice vectors, owing to a competition between directional locking and spatial velocity variations.