Ultrasound enhanced diffusion in hydrogels: An experimental and non-equilibrium molecular dynamics study.

Focused ultrasound has experimentally been found to enhance the diffusion of nanoparticles; our aim with this work is to study this effect closer using both experiments and non-equilibrium molecular dynamics. Measurements from single particle tracking of 40 nm polystyrene nanoparticles in an agarose hydrogel with and without focused ultrasound are presented and compared with a previous experimental study using 100 nm polystyrene nanoparticles. In both cases, we observed an increase in the mean square displacement during focused ultrasound treatment. We developed a coarse-grained non-equilibrium molecular dynamics model with an implicit solvent to investigate the increase in the mean square displacement and its frequency and amplitude dependencies. This model consists of polymer fibers and two sizes of nanoparticles, and the effect of the focused ultrasound was modeled as an external oscillating force field. A comparison between the simulation and experimental results shows similar mean square displacement trends, suggesting that the particle velocity is a significant contributor to the observed ultrasound-enhanced mean square displacement. The resulting diffusion coefficients from the model are compared to the diffusion equation for a two-time continuous time random walk. The model is found to have the same frequency dependency. At lower particle velocity amplitude values, the model has a quadratic relation with the particle velocity amplitude as described by the two-time continuous time random walk derived diffusion equation, but at higher amplitudes, the model deviates, and its diffusion coefficient reaches the non-hindered diffusion coefficient. This observation suggests that at higher ultrasound intensities in hydrogels, the non-hindered diffusion coefficient can be used.

Whole-genome detection using multivalent DNA-coated colloids.

To minimize the incorrect use of antibiotics, there is a great need for rapid and inexpensive tests to identify the pathogens that cause an infection. The gold standard of pathogen identification is based on the recognition of DNA sequences that are unique for a given pathogen. Here, we propose and test a strategy to develop simple, fast, and highly sensitive biosensors that make use of multivalency. Our approach uses DNA-functionalized polystyrene colloids that distinguish pathogens on the basis of the frequency of selected short DNA sequences in their genome. Importantly, our method uses entire genomes and does not require nucleic acid amplification. Polystyrene colloids grafted with specially designed surface DNA probes can bind cooperatively to frequently repeated sequences along the entire genome of the target bacteria, resulting in the formation of large and easily detectable colloidal aggregates. Our detection strategy allows "mix and read" detection of the target analyte; it is robust and highly sensitive over a wide concentration range covering, in the case of our test target genome Escherichia coli bl21-de3, 10 orders of magnitude from [Formula: see text] to [Formula: see text] copies/mL. The sensitivity compares well with state-of-the-art sensing techniques and has excellent specificity against nontarget bacteria. When applied to real samples, the proposed technique shows an excellent recovery rate. Our detection strategy opens the way to developing a robust platform for pathogen detection in the fields of food safety, disease control, and environmental monitoring.

Dynamic Light Scattering Based Microrheology of End-Functionalised Triblock Copolymer Solutions.

Nano-sized particles functionalised with short single-stranded (ss)DNAs can act as detectors of complementary DNA strands. Here we consider tri-block-copolymer-based, self-assembling DNA-coated nanoparticles. The copolymers are chemically linked to the DNA strands via azide (N3) groups. The micelles aggregate when they are linked with complementary ssDNA. The advantage of such block-copolymer-based systems is that they are easy to make. Here we show that DNA functionalisation results in inter-micellar attraction, but that N3-groups that have not reacted with the DNA detector strands also change the phase behaviour of the tri-block polymer solution. We studied the triblock copolymer, Pluronic® F108, which forms spherical micelles in aqueous solutions upon heating. We find that the triblock chains ending with either an N3 or N3-DNA complex show a dramatic change in phase behaviour. In particular, the N3-functionalisation causes the chain ends to cluster below the critical micelle temperature (CMT) of pure F108, forming flower-micelles with the N3-groups at the core, while the PPO groups are exposed to the solvent. Above the CMT, we see an inversion with the PPO chains forming the micellar core, while the N3-groups are now aggregating on the periphery, inducing an attraction between the micelles. Our results demonstrate that, due to the two competing self-assembling mechanisms, the system can form transient hydrogels.

Bulk rheology of sticky DNA-functionalized emulsions.

We measure by experiment and particle-based simulation the rheology of concentrated, non-Brownian droplet emulsions functionalized with surface-bound single-stranded (ss), "sticky," DNA. In the absence of ssDNA, the emulsion viscosity increases with the dispersed phase volume fraction ϕ, before passing through a liquid-solid transition at a critical ϕ_{c} related to random close packing. Introducing ssDNA leads to a liquid-solid transition at ϕ<ϕ_{c}, the onset being set by the droplet valency N and the ssDNA concentration (or simulated binding strength ε). Using insight from simulation, we identify three key behaviors: (i) jammed suspensions (ϕ>ϕ_{c}≈0.64) show weak effects of functionalization, with elastic rheology instead governed by droplet stiffness; (ii) suspensions with ϕ<ϕ_{c} and N=1, 2 always exhibit viscous rheology, regardless of functionalization; and (iii) for ϕ<ϕ_{c} and N>3, functionalization leads to a controllable viscous-elastic transition. We present state diagrams showing the range of rheological tuning attainable by these means.

Elastic response of wire frame glasses. I. Two dimensional model.

We study the elastic response of concentrated suspensions of rigid wire frame particles to a step strain. These particles are constructed from infinitely thin, rigid rods of length L. We specifically compare straight rod-like particles to bent and branched wire frames. In dense suspensions, the wire frames are frozen in a disordered state by the topological entanglements between their arms. We present a simple, geometric method to find the scaling of the elastic stress with concentration in these glassy systems. We apply this method to a simple 2D model system where a test particle is placed on a plane and constrained by a random distribution of points with number density ν. Two striking differences between wire frame and rod suspensions are found: (1) The linear elasticity per particle for wire frames is very large, scaling like ν2L4, whereas for rods, it is much smaller and independent of concentration. (2) Rods always shear thin but wire frames shear harden for concentrations less than ∼K/kBTL4, where K is the bending modulus of the particles. The deformation of wire frames is found to be important even for small strains, with the proportion of deformed particles at a particular strain, γ, being given by (νL2)2γ2. Our results agree well with simple numerical calculations for the 2D system.

Elastic response of wire frame glasses. II. Three-dimensional systems.

We study the elastic response of rigid wire frame particles in concentrated glassy suspensions to a step strain by applying the simple geometric methods developed in Paper I. The wire frame particles are comprised of thin rigid rods of length L, and their number density, ρ, is such that ρL3 ≫ 1. We specifically compare rigid rods to L-shapes made of two equal length rods joined at right angles. The behavior of wire frames is found to be strikingly different from that of rods. The linear elasticity scales like ρ3L6 for L-shaped particles, whereas it scales proportional to ρ for rods and the non-linear response shows a transition from shear hardening to shear softening at a critical density ρc∼K/kBTL6, where K is the bending modulus of the particles. For realistic particles made of double stranded DNA, this transition occurs at densities of about ρL3 ∼ 10. The reason for these differences is that wire frames can be forced to bend by the entanglements with their surroundings, whereas rods always remain straight. This is found to be very important even for small strains, with most particles being bent above a critical strain γc∼ρL3 -1.

Particle shapes leading to Newtonian dilute suspensions.

It is well known that suspensions of particles in a viscous fluid can affect the rheology significantly, producing a pronounced non-Newtonian response even in dilute suspension. However, it is unclear a priori which particle shapes lead to this behavior. We present two simple symmetry conditions on the shape which are sufficient for a dilute suspension to be Newtonian for all strain sizes and one sufficient for Newtonian behavior for small strains. We also construct a class of shapes out of thin, rigid rods not found by the symmetry argument which share this property for small strains.

Osmotic-Pressure-Induced Nematic Ordering in Suspensions of Laponite and Carboxy Methyl Cellulose.

Laponite is a synthetic clay that is known to form gels in aqueous suspensions at low concentrations (0.01 g/cm3). Although it is expected to form lyotropic liquid crystals, such phases usually do not form, as a consequence of laponite's tendency to form gels at concentrations below the threshold for liquid crystal formation. Here we show that macroscopic, birefringent phases of laponite can be prepared through osmotic compression of a laponite solution by an aqueous solution of carboxy methyl cellulose (CMC). We present polarization imaging studies showing how the initially dilute, isotropic laponite phase shrinks while developing typical birefringence colors between crossed polarizers. Using the Michel-Lévy interference charts, we were able to extract the refractive index and orientation of the laponite nanodisks in the compressed region. Our observations allow us to propose a tentative state diagram, indicating the concentration regions for which we obtain optically anisotropic gels.

Controlled Optofluidic Crystallization of Colloids Tethered at Interfaces.

We report experiments that show rapid crystallization of colloids tethered to an oil-water interface in response to laser illumination. This light-induced transition is due to a combination of long-ranged thermophoretic pumping and local optical binding. We show that the flow-induced force on the colloids can be described as the gradient of a potential. The nonequilibrium steady state due to local heating thus admits an effective equilibrium description. The optofluidic manipulation explored in this work opens novel ways to manipulate and assemble colloidal particles.

Computational design of probes to detect bacterial genomes by multivalent binding.

Rapid methods for diagnosis of bacterial infections are urgently needed to reduce inappropriate use of antibiotics, which contributes to antimicrobial resistance. In many rapid diagnostic methods, DNA oligonucleotide probes, attached to a surface, bind to specific nucleotide sequences in the DNA of a target pathogen. Typically, each probe binds to a single target sequence; i.e., target-probe binding is monovalent. Here we show using computer simulations that the detection sensitivity and specificity can be improved by designing probes that bind multivalently to the entire length of the pathogen genomic DNA, such that a given probe binds to multiple sites along the target DNA. Our results suggest that multivalent targeting of long pieces of genomic DNA can allow highly sensitive and selective binding of the target DNA, even if competing DNA in the sample also contains binding sites for the same probe sequences. Our results are robust to mild fragmentation of the bacterial genome. Our conclusions may also be relevant for DNA detection in other fields, such as disease diagnostics more broadly, environmental management, and food safety.

Transparent Films Made of Highly Scattering Particles.

Today, colloids are widely employed in various products from creams and coatings to electronics. The ability to control their chemical, optical, or electronic features by controlling their size and shape explains why these materials are so widely preferred. Nevertheless, altering some of these properties may also lead to some undesired side effects, one of which is an increase in optical scattering upon concentration. Here, we address this strong scattering issue in films made of binary colloidal suspensions. In particular, we focus on raspberry-type polymeric particles made of a spherical polystyrene core decorated by small hemispherical domains of acrylate with an overall positive charge, which display an unusual stability against aggregation in aqueous solutions. Their solid films display a brilliant red color due to Bragg scattering but appear completely white on account of strong scattering otherwise. To suppress the scattering and induce transparency, we prepared films by hybridizing them with oppositely charged PS particles with a size similar to that of the bumps on the raspberries. We report that the smaller PS particles prevent raspberry particle aggregation in solid films and suppress scattering by decreasing the spatial variation of the refractive index inside the film. We believe that the results presented here provide a simple strategy to suppress strong scattering of larger particles to be used in optical coatings.

On the role of flexibility in linker-mediated DNA hydrogels.

Three-dimensional DNA networks, composed of tri- or higher valent nanostars with sticky, single-stranded DNA overhangs, have been previously studied in the context of designing thermally responsive, viscoelastic hydrogels. In this work, we use linker-mediated gels, where the sticky ends of two trivalent nanostars are connected through the complementary sticky ends of a linear DNA duplex. We can design this connection to be either rigid or flexible by introducing flexible, non-binding bases. The additional flexibility provided by these non-binding bases influences the effective elasticity of the percolating gel formed at low temperatures. Here we show that by choosing the right length of the linear duplex and non-binding flexible joints, we obtain a completely different phase behaviour to that observed for rigid linkers. In particular, we use dynamic light scattering as a microrheological tool to monitor the self-assembly of DNA nanostars with linear linkers as a function of temperature. While we observe classical gelation when using rigid linkers, the presence of flexible joints leads to a cluster fluid with a much-reduced viscosity. Using both the oxDNA model and a coarse-grained simulation to investigate the nanostar-linker topology, we hypothesise on the possible structure formed by the DNA clusters. Moreover, we present a systematic study of the strong viscosity increase of aqueous solutions in the presence of these DNA building blocks.

Thermophoretic forces on a mesoscopic scale.

We use a mesoscale-molecular simulation technique known as Multi-Particle Collision Dynamics (MPC) to study the forces acting on a stationary colloid inside a temperature gradient. We compare our measurements of the thermophoretic force to a theoretical prediction based on Onsager's reciprocal relations, assuming that the temperature gradient is constant across the colloid. We find a good agreement between our measurements and theoretical predictions over a wide range of system parameters, even when the condition of uniform gradients is not strictly fulfilled. Our measurements further suggest that the magnitude of the thermophoretic force depends on the hydrodynamic boundary condition at the colloidal surface, thus highlighting the hydrodynamic character of colloidal thermophoresis. We also investigate how fluid advection disturbs the interfacial layer around the colloid and introduce a dimensionless number to quantify the validity of local thermodynamic equilibrium.

Unexpected stability of aqueous dispersions of raspberry-like colloids.

Aqueous colloidal suspensions, both man-made and natural, are part of our everyday life. The applicability of colloidal suspensions, however, is limited by the range of conditions over which they are stable. Here we report a novel type of highly monodisperse raspberry-like colloids, which are prepared in a single-step synthesis that relies on simultaneous dispersion and emulsion polymerisation. The resulting raspberry colloids behave almost like hard spheres. In aqueous solutions, such prepared raspberries show unexpected stability against aggregation over large variations of added salt concentrations without addition of stabilisers. We present simple Derjaguin-Landau-Verwey-Overbeek (DLVO) calculations performed on raspberry-like and smooth colloids showing that this stability results from our raspberries' unique morphology, which extends our understanding of colloidal stability against salting. Further, the raspberries' stability facilitates the formation of superspheres and thin films in which the raspberry colloids self-assemble into hexagonally close-packed photonic crystals with exquisite reproducibility.

DNA-Coated Functional Oil Droplets.

Many industrial soft materials include oil-in-water (O/W) emulsions at the core of their formulations. By using tuneable interface stabilizing agents, such emulsions can self-assemble into complex structures. DNA has been used for decades as a thermoresponsive, highly specific binding agent between hard and, recently, soft colloids. Up until now, emulsion droplets functionalized with DNA had relatively low coating densities and were expensive to scale up. Here, a general O/W DNA-coating method using functional nonionic amphiphilic block copolymers, both diblock and triblock, is presented. The hydrophilic poly(ethylene glycol) ends of the surfactants are functionalized with azides, allowing for efficient, dense, and controlled coupling of dibenzocyclooctane-functionalized DNA to the polymers through a strain-promoted alkyne-azide click reaction. The protocol is readily scalable due to the triblock's commercial availability. Different production methods (ultrasonication, microfluidics, and membrane emulsification) are used with different oils (hexadecane and silicone oil) to produce functional droplets in various size ranges (submicron, ∼20 and >50 µm), showcasing the generality of the protocol. Thermoreversible submicron emulsion gels, hierarchical "raspberry" droplets, and controlled droplet release from a flat DNA-coated surface are demonstrated. The emulsion stability and polydispersity is evaluated using dynamic light scattering and optical microscopy. The generality and simplicity of the method opens up new applications in soft matter, biotechnological research, and industrial advances.

Microrheology of DNA hydrogels.

A key objective in DNA-based material science is understanding and precisely controlling the mechanical properties of DNA hydrogels. We perform microrheology measurements using diffusing wave spectroscopy (DWS) to investigate the viscoelastic behavior of a hydrogel made of Y-shaped DNA (Y-DNA) nanostars over a wide range of frequencies and temperatures. We observe a clear liquid-to-gel transition across the melting temperature region for which the Y-DNA bind to each other. Our measurements reveal a cross-over between the elastic [Formula: see text] and loss modulus [Formula: see text] around the melting temperature [Formula: see text] of the DNA building blocks, which coincides with the systems percolation transition. This transition can be easily shifted in temperature by changing the DNA bond length between the Y shapes. Using bulk rheology as well, we further show that, by reducing the flexibility between the Y-DNA bonds, we can go from a semiflexible transient network to a more energy-driven hydrogel with higher elasticity while keeping the microstructure the same. This level of control in mechanical properties will facilitate the design of more sensitive molecular sensing tools and controlled release systems.

A unified description of colloidal thermophoresis.

We use the dynamic length and time scale separation in suspensions to formulate a general description of colloidal thermophoresis. Our approach allows an unambiguous definition of separate contributions to the colloidal flux and clarifies the physical mechanisms behind non-equilibrium motion of colloids. In particular, we derive an expression for the interfacial force density that drives single-particle thermophoresis in non-ideal fluids. The issuing relations for the transport coefficients explicitly show that interfacial thermophoresis has a hydrodynamic character that cannot be explained by a purely thermodynamic consideration. Our treatment generalises the results from other existing approaches, giving them a clear interpretation within the framework of non-equilibrium thermodynamics.

Colloidal motion under the action of a thermophoretic force.

We present thermophoretic measurements in aqueous suspensions of three different polystyrene (PS) particles of varying negative charge, size, and surface coating. Our measurement technique is based on the observation of the colloidal steady-state distribution using conventional bright-field microscopy, which avoids undesirable effects such as laser-induced convection or local heating. We find that the colloids with the weakest zeta potential exhibit the strongest thermophoretic effect, suggesting that the Soret coefficient has a more intricate dependence on surface functionality than predicted by existing theoretical approaches. We also study the relaxation of the colloids to steady-state and propose a model to quantify the relaxation speed, based on the time evolution of the colloidal center of mass. Our observations are well described by this model and show that the relaxation speed tends to increase with the magnitude of the thermophoretic force.

Oscillatory rheology of dense, athermal suspensions of nearly hard spheres below the jamming point.

The viscosity of a dense suspension has contributions from hydrodynamics and particle interactions, both of which depend upon the flow-induced arrangement of particles into fragile structures. Here, we study the response of nearly hard sphere suspensions to oscillatory shear using simulations and experiments in the athermal, non-inertial limit. Three distinct regimes are observed as a function of the strain amplitude γ0. For γ0 < 10-1, initially non-contacting particles remain separated and the suspension behaves similarly to a Newtonian fluid, with the shear stress proportional to the strain rate, and the normal stresses close to zero. For γ0 > 101, the microstructure becomes well-established at the beginning of each shear cycle and the rheology is quasi-Newtonian: the shear stress varies with the rate, but flow-induced structures lead to non-zero normal stresses. At intermediate γ0, particle-particle contacts break and reform across entire oscillatory cycles, and we probe a non-linear regime that reveals the fragility of the material. Guided by these features, we further show that oscillatory shear may serve as a diagnostic tool to isolate specific stress contributions in dense suspensions, and more generally in those materials whose rheology has contributions with both hydrodynamic and non-hydrodynamic origin.

Phase behaviour in complementary DNA-coated gold nanoparticles and fd-viruses mixtures: a numerical study.

A new gel-forming colloidal system based on a binary mixture of fd-viruses and gold nanoparticles functionalized with complementary DNA single strands has been recently introduced. Upon quenching below the DNA melt temperature, such a system results in a highly porous gel state, that may be developed in a new functional material of tunable porosity. In order to shed light on the gelation mechanism, we introduce a model closely mimicking the experimental one and we explore via Monte Carlo simulations its equilibrium phase diagram. Specifically, we model the system as a binary mixture of hard rods and hard spheres mutually interacting via a short-range square-well attractive potential. In the experimental conditions, we find evidence of a phase separation occurring either via nucleation-and-growth or via spinodal decomposition. The spinodal decomposition leads to the formation of small clusters of bonded rods and spheres whose further diffusion and aggregation leads to the formation of a percolating network in the system. Our results are consistent with the hypothesis that the mixture of DNA-coated fd-viruses and gold nanoparticles undergoes a non-equilibrium gelation via an arrested spinodal decomposition mechanism.