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The article focuses on multicellular cancer spheroids in vitro model that replicates many features of solid tumors in vivo. It mentions that biomimetic hydrogel scaffolds for MCS growth recapitulate the behavior of natural extracellular matrix, essential for regulating cancer cell behavior. It further review the use of different types of hydrogels for MCS growth.

We review recent progress in the development of polymer nanostructured materials with periodic structures and compositions having applications in photonics and optical data storage. This review provides a brief description of the microfabrication and self-assembly methods used for the production of polymer materials with periodic structures, and highlights the properties and applications of photonic materials derived from block copolymers, colloid crystals, and microfabricated polymers. We conclude with a summary of current and future research efforts and opportunities in the development of polymer materials for photonic applications. [Copyright &y& Elsevier]

Studies the liquid-to-solid transition of a simple model liquid confined between two surfaces as a function of surface separation. Decrease of separation corresponding to seven molecular layers; Display of liquid-like shear viscosity; Transition to a solid.

Focuses the reduction in the effective frictional forces between solid surfaces bearing polymer brushes. Use of lubricants to reduce friction and wear between rubbing surfaces; Tethering polymer chains to the surfaces; Profiles measured between mica surfaces; Long-ranged repulsion between the brushes.

Fibrous networks formed by biological polymers such as collagen or fibrin exhibit nonlinear mechanical behavior. They undergo strong stiffening in response to weak shear and elongational strains, but soften under compressional strain, in striking difference with the response to the deformation of flexible-strand networks formed by molecules. The nonlinear properties of fibrous networks are attributed to the mechanical asymmetry of the constituent filaments, for which a stretching modulus is significantly larger than the bending modulus. Studies of the nonlinear mechanical behavior are generally performed on hydrogels formed by biological polymers, which offers limited control over network architecture. Here, we report an engineered covalently cross-linked nanofibrillar hydrogel derived from cellulose nanocrystals and gelatin. The variation in hydrogel com)position provided a broad-range change in its shear modulus. The hydrogel exhibited both shear-stiffening and compression-induced softening, in agreement with the predictions of the affine model. The threshold nonlinear stress and strain were universal for the hydrogels with different compositions, which suggested that nonlinear mechanical properties are general for networks formed by rigid filaments. The experimental results were in agreement with an affine model describing deformation of the network formed by rigid filaments. Our results lend insight into the structural features that govern the nonlinear biomechanics of fibrous networks and provide a platform for future studies of the biological impact of nonlinear mechanical properties. [ABSTRACT FROM AUTHOR]

This review describes the most recent progress in the use of polymer multiresponsive microgels as central components of advanced, functional colloidal materials. Significant areas of development include the use of microgels as microreactors for templated synthesis of inorganic nanoparticles with predetermined properties, as optically active materials including lenses and photonic crystals, and as primary units in site-specific and controlled drug delivery systems. In the last category, both synthetic and biopolymeric microgels are discussed. [ABSTRACT FROM AUTHOR]

Gene expression analysis of individual cells enables characterization of heterogeneous and rare cell populations, yet widespread implementation of existing single-cell gene analysis techniques has been hindered due to limitations in scale, ease, and cost. Here, we present a novel microdroplet-based, one-step reverse-transcriptase polymerase chain reaction (RT-PCR) platform and demonstrate the detection of three targets simultaneously in over 100,000 single cells in a single experiment with a rapid read-out. Our customized reagent cocktail incorporates the bacteriophage T7 gene 2.5 protein to overcome cell lysate-mediated inhibition and allows for one-step RT-PCR of single cells encapsulated in nanoliter droplets. Fluorescent signals indicative of gene expressions are analyzed using a probabilistic deconvolution method to account for ambient RNA and cell doublets and produce single-cell gene signature profiles, as well as predict cell frequencies within heterogeneous samples. We also developed a simulation model to guide experimental design and optimize the accuracy and precision of the assay. Using mixtures of in vitro transcripts and murine cell lines, we demonstrated the detection of single RNA molecules and rare cell populations at a frequency of 0.1%. This low cost, sensitive, and adaptable technique will provide an accessible platform for high throughput single-cell analysis and enable a wide range of research and clinical applications. [ABSTRACT FROM AUTHOR]

The article discusess a study conducted for achieving precise organization of nanoparticles (NPs) in three-dimensional space. It examines morphogenesis of nanoparticle assemblies and a cholesteric liquid crystalline host formed by cellulose nanocrystals for experiencing marked changes in shape and structure as a function of concentration. It mentions increase in NP loading triggers reversible droplet transformation to gain a core-shell morphology with an isotropic core.

An important goal of the modern soft matter science is to discover new self-assembly modalities to precisely control the placement of small particles in space. Spatial inhomogeneity of liquid crystals offers the capability to organize colloids in certain regions such as the cores of the topological defects. Here we report two self-assembly modes of nanoparticles in linear defects-disclinations in a lyotropic colloidal cholesteric liquid crystal: a continuous helicoidal thread and a periodic array of discrete beads. The beads form one-dimensional arrays with a periodicity that matches half a pitch of the cholesteric phase. The periodic assembly is governed by the anisotropic surface tension and elasticity at the interface of beads with the liquid crystal. This mode of self-assembly of nanoparticles in disclinations expands our ability to use topological defects in liquid crystals as templates for the organization of nanocolloids. [ABSTRACT FROM AUTHOR]

We build on the concept of hot intrusion embossing to develop a one-step fabrication method for thermoplastic microfluidic channels containing integrated three-dimensional features. This was accomplished with simple, rapid-to-fabricate imprint templates containing microcavities that locally control the intrusion of heated thermoplastic based on their cross-sectional geometries. The use of circular, rectangular and triangular cavity geometries was demonstrated for the purposes of forming posts, multi-focal length microlense arrays, walls, steps, tapered features and three-dimensional serpentine microchannels. Process variables, such as temperature and pressure, controlled feature dimensions without affecting the overall microchannel geometry. The approach was demonstrated for polycarbonate, cycloolefin copolymer and polystyrene, but in principle is applicable to any thermoplastic. The approach is a step forward towards rapid fabrication of complex, robust, microfluidic platforms with integrated multi-functional elements. [ABSTRACT FROM AUTHOR]

Microscale technologies offer the capability to generate in vitro artificial cellular microenvironments that recapitulate the spatial, biochemical, and biophysical characteristics of the native extracellular matrices and enable systematic, quantitative, and high-throughput studies of cell fate in their respective environments. We developed a microfluidic platform for the generation of two-dimensional arrays of micrometer-size cell-laden hydrogel modules (HMs) for cell encapsulation and culture. Fibroblast cells (NIH 3T3) and non-adherent T cells (EL4) encapsulated in HMs showed high viability and proliferation. The platform was used for real-time studies of the effect of spatial constraints and structural and mechanical properties of HMs on cell growth, both on the level of individual cells. Due to the large number of cellladen HMs and stochastic cell distribution, cell studies were conducted in a time- and labor efficient manner. The platform has a broad range of applications in the exploration of the role of chemical and biophysical cues on individual cells, studies of in vitro cell migration, and the examination of cell-extracellular matrix and cell-cell interactions. [ABSTRACT FROM AUTHOR]

Nanoparticle (NP) dispersions are extensively used for the producing nanocomposite materials. Optimization of formulations of NP dispersions is a time- and labor-consuming process that can benefit from high-throughput preparation of composite materials, followed by studies of their structure-property relationships. This paper describes a microfluidic platform for producing photopolymerized films from NP-monomer dispersions. The platform enables rapid and reproducible preparation of films with varying compositions by tuning the flow rates of the monomer and NP-monomer mixtures, along with suppressed evaporation of volatile monomers, no need of an inert atmosphere, and the reduced exposure to potentially harmful monomers and NPs. This work paves the way for efficient studies of composition-dependent properties of nanocomposite materials. [ABSTRACT FROM AUTHOR]

A similarity between chemical reactions and self-assembly of nanoparticles offers a strategy that can enrich both the synthetic chemistry and the nanoscience fields. Synthetic methods should enable quantitative control of the structural characteristics of nano-particle ensembles such as their aggregation number or directionality, whereas the capability to visualize and analyze emerging nanostructures using characterization tools can provide insight into intelligent molecular design and mechanisms of chemical reactions. We explored this twofold concept for an exemplary system including the polymerization of bifunctional nanoparticles in the presence of monofunctional colloidal chain stoppers. Using reaction-specific design rules, we synthesized chain stoppers with controlled reactivity and achieved quantitative fine-tuning of the self-assembled structures. Analysis of the nanostructures provided information about polymerization kinetics, side reactions, and the distribution of all of the species in the reaction system. A quantitative model was developed to account for the reactivity, kinetics, and side reactions of nanoparticles, all governed by the design of colloidal chain stoppers. This work provided the ability to test theoretical models developed for molecular polymerization. [ABSTRACT FROM AUTHOR]

Hydrogels are networks of hydrophilic polymer chains that are swollen with water, and they are useful for a wide range of applications because they provide stable niches for immobilizing proteins and cells. We report here the marriage of hydrogels with digital microfluidic devices. Until recently, digital microfluidics, a fluid handling technique in which discrete droplets are manipulated electromechanically on the surface of an array of electrodes, has been used only for homogeneous systems involving liquid reagents. Here, we demonstrate for the first time that the cylindrical hydrogel discs can be incorporated into digital microfluidic systems and that these discs can be systematically addressed by droplets of reagents. Droplet movement is observed to be unimpeded by interaction with the gel discs, and gel discs remain stationary when droplets pass through them. Analyte transport into gel discs is observed to be identical to diffusion in cases in which droplets are incubated with gels passively, but transport is enhanced when droplets are continually actuated through the gels. The system is useful for generating integrated enzymatic microreactors and for three-dimensional cell culture. This paper demonstrates a new combination of techniques for lab-on-a-chip systems which we propose will be useful for a wide range of applications. [ABSTRACT FROM AUTHOR]

Abstract: Elasticity of cellular microenvironments strongly influences cell motility, phagocytosis, growth and differentiation. Currently, the relationship between the cell behaviour and matrix stiffness is being studied for cells seeded on planar substrates, however in three-dimensional (3D) microenvironments cells may experience mechanical signalling that is distinct from that on a two-dimensional matrix. We report a microfluidic approach for high-throughput generation of 3D microenvironments with different elasticity for studies of cell fate. The generation of agarose microgels with different elastic moduli was achieved by (i) introducing into a microfluidic droplet generator two streams of agarose solutions, one with a high concentration of agarose and the other one with a low concentration of agarose, at varying relative volumetric flow rate ratios of the two streams, and (ii) on-chip gelation of the precursor droplets. At 37 °C, the method enabled a ∼35-fold variation of the shear elastic modulus of the agarose gels. The application of the method was demonstrated by encapsulating two mouse embryonic stem cell lines within the agarose microgels. This work establishes a foundation for the high-throughput generation of combinatorial microenvironments with different mechanical properties for cell studies. [Copyright &y& Elsevier]

This article reviews recent developments in the microfluidic preparation of different types of particles made of polymeric and inorganic materials. We discuss control of the particle sizes, morphologies, shapes, and structures in terms of various features of microfluidic synthesis. [ABSTRACT FROM AUTHOR]

Self-organization of nanoparticles is an efficient strategy for producing nanostructures with complex, hierarchical architectures. The past decade has witnessed great progress in nanoparticle self-assembly, yet the quantitative prediction of the architecture of nanoparticle ensembles and of the kinetics of their formation remains a challenge. We report on the marked similarity between the self-assembly of metal nanoparticles and reaction-controlled step-growth polymerization. The nanoparticles act as multifunctional monomer units, which form reversible, noncovalent bonds at specific bond angles and organize themselves into a colloidal polymer. We show that the kinetics and statistics of step-growth polymerization enable a quantitative prediction of the architecture of linear, branched, and cyclic self-assembled nanostructures; their aggregation numbers and size distribution; and the formation of structural isomers. [ABSTRACT FROM AUTHOR]

Abstract: Since the inception of soft lithography, microfluidic devices for cardiovascular research have been fabricated easily and cost-effectively using the soft lithography method. The drawback of this method was the fabrication of microchannels with rectangular cross-sections, which did not replicate the circular cross-sections of blood vessels. This article presents a novel, straightforward approach for the fabrication of microchannels with circular cross-sections in poly(dimethylsiloxane) (PDMS), using soft lithography. The method exploits the polymerization of the liquid silicone oligomer around a gas stream when both of them are coaxially introduced in the microchannel with a rectangular cross-section. We demonstrate (i) the ability to control the diameter of circular cross-sections of microchannels from ca. 40–100 μm; (ii) the fabrication of microchannels with constrictions, and (iii) the capability to grow endothelial cells on the inner surface of the microchannels. [Copyright &y& Elsevier]

We studied the optical properties of hybrid multilayer microspheres (HMMs). We prepared multilayer particles with alternating radial layers of gold nanoparticles (NPs) and poly(methyl methacrylate) and achieved control over particle size, the thickness of particle layers, and the surface coverage of gold NPs. We showed the ability to tune the spectral characteristics of the HMMs, which was based on frequency dispersion of the dielectric constant of polymer–metal NP structures. Good agreement between experimental and theoretical extinction properties of the HMMs was obtained. In comparison with multilayer structures synthesized solely from polymers, hybrid multilayer microspheres have a larger refractive layer contrast between adjacent layers, which is important for practical applications in optoelectronic devices. [ABSTRACT FROM AUTHOR]

Abstract: We present a straightforward, accessible method to covalently pattern proteins in poly(dimethyl siloxane) (PDMS) microchannels. Our approach includes (i) region-specific photografting of a layer of poly(acrylamide) (PAAm) and (ii) bioconjugation of PAAm with a desired protein. The method produces symmetric protein patterns on all channel walls, which have high specificity and pattern fidelity, are compatible with a variety of geometries and exhibit excellent longevity under shear stresses of up to 1dyn/cm. We demonstrate the generality of the method by creating multi-protein gradients within microfluidic microchannels and by in-situ patterning of islands of multiple proteins. Protein activity was observed by the digestion of BODIPY–casein using channels patterned with trypsin. [Copyright &y& Elsevier]

In vivo, stem cell fate is regulated by local microenvironmental parameters. Governing parameters in this stem cell niche include soluble factors, extra-cellular matrix, and cell-cell interactions. The complexity of this in vivo niche limits analyses into how individual niche parameters regulate stem cell fate. Herein we use mouse embryonic stem cells (mESC) and microcontact printing (μCP) to investigate how niche size controls endogenous signaling thresholds. mCP is used to restrict colony diameter, separation, and degree of clustering. We show, for the first time, spatial control over the activation of the Janus kinase/signal transducer and activator of transcription pathway (Jak-Stat). The functional consequences of this niche-sizedependent signaling control are confirmed by demonstrating that direct and indirect transcriptional targets of Stat3, including members of the Jak-Stat pathway and pluripotency-associated genes, are regulated by colony size. Modeling results and empirical observations demonstrate that colonies less than 100 μm in diameter are too small to maximize endogenous Stat3 activation and that colonies separated by more than 400 μm can be considered independent from each other. These results define parameter boundaries for the use of ESCs in screening studies, demonstrate the importance of context in stem cell responsiveness to exogenous cues, and suggest that niche size is an important parameter in stem cell fate control. [ABSTRACT FROM AUTHOR]

Complexity in the spatial organization of human embryonic stem cell (hESC) cultures creates heterogeneous microenvironments (niches) that influence hESC fate. This study demonstrates that the rate and trajectory of hESC differentiation can be controlled by engineering hESC niche properties. Niche size and composition regulate the balance between differentiation-inducing and -inhibiting factors. Mechanistically, a niche size-dependent spatial gradient of Smad1 signaling is generated as a result of antagonistic interactions between hESCs and hESC-derived extra-embryonic endoderm (ExE). These interactions are mediated by the localized secretion of bone morphogenetic protein-2 (BMP2) by ExE and its antagonist, growth differentiation factor-3 (GDF3) by hESCs. Micropatterning of hESCs treated with small interfering (si) RNA against GDF3, BMP2 and Smad1, as well treatments with a Rho-associated kinase (ROCK) inhibitor demonstrate that independent control of Smad1 activation can rescue the colony size-dependent differentiation of hESCs. Our results illustrate, for the first time, a role for Smad1 in the integration of spatial information and in the niche-size-dependent control of hESC self-renewal and differentiation. [ABSTRACT FROM AUTHOR]

Heterocoagulation of large and small oppositely charged colloid particles, accompanied by spreading of small beads over the surface of large spheres, offers a promising alternative to synthesis of core–shell particles via interfacial polymerization. In this paper, conditions required for complete spreading of the shell-forming polymer over the surface of the core-forming material (CFM) are predicted in terms of a critical distance, xcr, between the small particles on the surface of the CFM. The theoretical value of xcr is tested in experiments conducted for polypyrrole/polyacrylic and silica-titanyl sulfate/polyacrylic heterocoagulate units. [Copyright &y& Elsevier]

Flow of soft matter objects through one-dimensional environments is important in industrial, biological and biomedical systems. Establishing the underlying principles of the behavior of soft matter in confinement can shed light on its performance in many man-made and biological systems. Here, we report an experimental and theoretical study of translocation of micrometer-size hydrogels (microgels) through microfluidic channels with a diameter smaller than an unperturbed microgel size. For microgels with different dimensions and mechanical properties, under a range of applied pressures, we established the universal principles of microgel entrance and passage through microchannels with different geometries, as well as the reduction in microgel volume in confinement. We also show a non-monotonic change in the flow rate of liquid through the constrained microgel, governed by its progressive confinement. The experimental results were in agreement with the theory developed for non-linear biaxial deformation of unentangled polymer gels. Our work has implications for a broad range of phenomena, including occlusion of blood vessels by thrombi and needle-assisted hydrogel injection in tissue engineering. [ABSTRACT FROM AUTHOR]