Plasmon-Free Polymeric Nanowrinkled Substrates for Surface-Enhanced Raman Spectroscopy of Two-Dimensional Materials.

We report plasmon-free polymeric nanowrinkled substrates for surface-enhanced Raman spectroscopy (SERS). Our simple, rapid, and cost-effective fabrication method involves depositing a poly(ethylene glycol)diacrylate (PEGDA) prepolymer solution droplet on a fully polymerized, flat PEGDA substrate, followed by drying the droplet at room conditions and plasma treatment, which polymerizes the deposited layer. The thin polymer layer buckles under axial stress during plasma treatment due to its different mechanical properties from the underlying soft substrate, creating hierarchical wrinkled patterns. We demonstrate the variation of the wrinkling wavelength with the drying polymer molecular weight and concentration (direct relations are observed). A transition between micron to nanosized wrinkles is observed at 5 v % concentration of the lower molecular-weight polymer solution (PEGDA Mn 250). The wrinkled substrates are observed to be reproducible, stable (at room conditions), and, especially, homogeneous at and below the transition regime, where nanowrinkles dominate, making them suitable candidates for SERS. As a proof-of-concept, the enhanced SERS performance of micro/nanowrinkled surfaces in detecting graphene and hexagonal boron nitride (h-BN) is illustrated. Compared to the SiO2/Si surfaces, the wrinkled PEGDA substrates significantly enhanced the signature Raman band intensities of graphene and h-BN by a factor of 8 and 50, respectively.

Interfacial Forces across Ionic Liquid Solutions: Effects of Ion Concentration and Water Domains †.

Using the surface force apparatus (SFA), the interaction forces between mica surfaces across ionic liquid (IL) solutions are studied. The IL solution, 1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide in propylene carbonate solvent, is used at different concentrations to elucidate the ions' conformation at the interface from the analysis of short-range structural forces. A direct correlation between the ion layer thickness at the interface and the IL molar fraction in the solution is observed, suggesting conformational changes relative to the ion packing density. In addition, effects of large microscopic and macroscopic water domains at the interface are investigated. The microscopic water domains induced significant adhesion at contact because of the long-range capillary forces, which are found to depend on solvent concentration. The macroscopic water domains entirely cover the interaction area, ensuring that the long-range interfacial interactions occur entirely across the aqueous electrolyte solution with dissolved IL ions as the electrolyte. These results help elucidate the interfacial interactions in IL-charged solid interfaces with practical importance in green energy storage, catalysis, and lubrication.

Deep Tissue Penetration of Bottle-Brush Polymers via Cell Capture Evasion and Fast Diffusion.

Drug nanocarriers (NCs) capable of crossing the vascular endothelium and deeply penetrating into dense tissues of the CNS could potentially transform the management of neurological diseases. In the present study, we investigated the interaction of bottle-brush (BB) polymers with different biological barriers in vitro and in vivo and compared it to nanospheres of similar composition. In vitro internalization and permeability assays revealed that BB polymers are not internalized by brain-associated cell lines and translocate much faster across a blood-brain barrier model compared to nanospheres of similar hydrodynamic diameter. These observations performed under static, no-flow conditions were complemented by dynamic assays performed in microvessel arrays on chip and confirmed that BB polymers can escape the vasculature compartment via a paracellular route. BB polymers injected in mice and zebrafish larvae exhibit higher penetration in brain tissues and faster extravasation of microvessels located in the brain compared to nanospheres of similar sizes. The superior diffusivity of BBs in extracellular matrix-like gels combined with their ability to efficiently cross endothelial barriers via a paracellular route position them as promising drug carriers to translocate across the blood-brain barrier and penetrate dense tissue such as the brain, two unmet challenges and ultimate frontiers in nanomedicine.

Electrostatic Screening Length in "Soft" Electrolyte Solutions.

Using the Surface Forces Apparatus on solutions of polymeric ions, the effect of specific ion-ion correlations is evaluated on the characteristic decay length, λ, of screened electrostatic interactions between charged surfaces. Electrolyte solutions composed of point charges surrounded by repulsive polymeric shells were used to elucidate the role of ions size and size asymmetry between co- and counterions on the screening of electrostatic forces. In electrolytes composed of large polymeric cations and small point-charge anions, because of the steric and excluded volume effects, the screening length follows the simple scaling relation λ ∼ d, where d is the characteristic size of the large cation. It is also reported that both co- and counterion sizes affect the thickness of the electrical double layer and influence the screened electrostatic interactions. In solutions of polymeric cation/anion pairs, the screening length is shown to depend on an asymmetry factor. These results provide insights into correlation effects in electrolytes, which were so far unreachable experimentally and help elucidate such effects in electronics, energy storage devices, and biomedical systems.

Chitosan hydrogel micro-bio-devices with complex capillary patterns via reactive-diffusive self-assembly.

We present chitosan hydrogel microfluidic devices with self-assembled complex microcapillary patterns, conveniently formed by a diffusion-reaction process. These patterns in chitosan hydrogels are formed by a single-step procedure involving diffusion of a gelation agent into the polymer solution inside a microfluidic channel. By changing the channel geometry, it is demonstrated how to control capillary length, trajectory and branching. Diffusion of nanoparticles (NPs) in the capillary network is used as a model to effectively mimic the transport of nano-objects in vascularized tissues. Gold NPs diffusion is measured locally in the hydrogel chips, and during their two-step transport through the capillaries to the gel matrix and eventually to embedded cell clusters in the gel. In addition, the quantitative analyses reported in this study provide novel opportunities for theoretical investigation of capillary formation and propagation during diffusive gelation of biopolymers. STATEMENT OF SIGNIFICANCE: Hydrogel micropatterning is a challenging task, which is of interest in several biomedical applications. Creating the patterns through self assembly is highly beneficial, because of the accessible and practical preparation procedure. In this study, we introduced complex self-assembled capillary patterns in chitosan hydrogels using a microfluidic approach. To demonstrate the potential application of these capillary patterns, a vascularized hydrogel with microwells occupied by cells was produced, and the diffusion of gold nanoparticles travelling in the capillaries and diffusing in the gel were evaluated. This model mimics a simplified biological tissue, where nanomedicine has to travel through the vasculature, extravasate into and diffuse through the extracellular matrix and eventually reach targeted cells.

Direct cell-cell communication with three-dimensional cell morphology on wrinkled microposts.

Cell-cell communication plays a critical role in a myriad of processes, such as homeostasis, angiogenesis, and carcinogenesis, in multi-cellular organisms. Monolayer cell models have notably improved our understanding of cellular interactions. However, the cultured cells on the planar surfaces adopt a two-dimensional morphology, which poorly imitates cellular organization in vivo, providing physiologically-irrelevant cell responses. Non-planar surfaces comprising various patterns have demonstrated great abilities in directing cellular growth and producing different cell morphologies. In recent years, a few topographical substrates have provided valuable information about cell-cell signalling, however, none of these studies have reported a three-dimensional (3D) cell morphology. Here, we introduce a structurally tunable topographical platform that can maintain cell coupling while inducing a true 3D cell morphology. Optical imaging and fluorescence recovery after photobleaching are used to illustrate these capabilities. Our analyses suggest that the intercellular signalling on the present platform, which we propose is mainly through gap junctions, is comparable to that in natural tissue. STATEMENT OF SIGNIFICANCE: A better understanding of direct cellular communication can help treating neurological diseases and cancers, which may be caused by dysfunctional intercellular signaling. To investigate cell-cell contact, cells are conventionally plated onto planar surfaces, where they flatten and adopt a two-dimensional cell morphology. These unrealistic models are physiologically-irrelevant since cells exhibit a three-dimensional (3D) shape in the body. Therefore, porous scaffolds and topographical surfaces, capable of inducing various cell morphologies, have been introduced, in which the latter is more desirable for sample imaging and screening. However, the few non-planar substrates used to study cell coupling have not produced a 3D cell shape. Here, we present a tunable culture platform that can control direct cell-cell communication while maintaining true 3D cell morphologies.