Microfluidic platforms for advanced risk assessments of nanomaterials.

In the past few years, promising efforts to utilize microfabrication-based technologies have laid the foundation for developing advanced, and importantly more physiologically-realistic, microfluidic methods for risk assessment of engineered nanomaterials (ENMs). In the present review, we discuss the wave of recent developments using microfluidic-based in vitro models and platforms for nanotoxicological assays, such as determination of cell viability, cellular dose, oxidative stress and nuclear damage. Here, we specifically highlight the tangible advantages of microfluidic devices in providing promising tools to tackle many of the current and ongoing challenges faced with traditional toxicology assays.

Enhanced upconversion luminescence in NaGdF4:Yb,Er nanocrystals by Fe3+ doping and their application in bioimaging.

The visible green and red upconversion emissions in Er(3+)/Yb(3+) doped β-NaGdF4 nanoparticles were enhanced by tridoping with Fe(3+) ions (0-40 mol%). XRD, XPS, ICP-AES and EDS data demonstrated successful incorporation of Fe(3+) ions in NaGdF4:Yb(3+)/Er(3+) nanoparticles. The effect of Fe(3+) tridoping on the upconversion luminescence in NaGdF4:Yb(3+)/Er(3+) NPs was investigated in detail.

Multiparametric assessment of Cd²+ cytotoxicity using MTT-based microfluidic image cytometry.

A modified MTT protocol-based microfluidic image cytometry (μFIC) was performed to assess Cd(2+) induced cytotoxicity. The expanded capabilities of μFIC, such as in situ measurement, high-throughput, and multiparametric analysis of adherent cells under precisely controlled chemical environments of microfluidic channels, were demonstrated in this study. Multiparametric analysis of μFIC data has enabled us to categorize the progress of cell death into at least four different subgroups based on their morphology and metabolic activity.

Integrated microfluidics platforms for investigating injury and regeneration of CNS axons.

We describe the development of experimental platforms to quantify the regeneration of injured central nervous system (CNS) neurons by combining engineering technologies and primary neuronal cultures. Although the regeneration of CNS neurons is an important area of research, there are no currently available methods to screen for drugs. Conventional tissue culture based on Petri dish does not provide controlled microenvironment for the neurons and only provide qualitative information.

Synthesis and evaluation of cytotoxic effects of hanultarin and its derivatives.

One of the known cytotoxic lignans is (-)-1-O-feruloyl-secoisolariciresinol designated as hanultarin, which was isolated from the seeds of Trichosanthes kirilowii. In this Letter, we described the first synthesis of 1-O-feruloyl-secoisolariciresinol, 1,4-O-diferuloyl-secoisolariceresinol and their analogues. The cytotoxicities of these compounds were evaluated against several cancer cell lines.

A new perspective on in vitro assessment method for evaluating quantum dot toxicity by using microfluidics technology.

In this study, we demonstrate a new perspective on in vitro assessment method for evaluating quantum dot (QD) toxicity by using microfluidics technology. A new biomimetic approach, based on the flow exposure condition, was applied in order to characterize the cytotoxic potential of QD. In addition, the outcomes obtained from the flow exposure condition were compared to those of the static exposure condition.

Assessment of cytocompatibility of surface-modified CdSe/ZnSe quantum dots for BALB/3T3 fibroblast cells.

With the widespread use of quantum dots (QDs), the likelihood of exposure to QDs has been assumed to have increased substantially. Recently, QDs have been employed in numerous biological and medical applications. However, there is a lack of toxicological data pertaining to QDs.

Morphology-based assessment of Cd2+ cytotoxicity using microfluidic image cytometry (microFIC).

Microfluidic systems have significant implications in the field of in vitro cell-based assays since they may allow conventional cell-based assays to be conducted in an automated and high-throughput fashion. In this study, we combined a simple microfluidic cells-on-chip system with a morphology-based image cytometric analysis approach for the assessment of Cd(2+) induced apoptosis of Chang liver cell line. A simple and efficient in situ monitoring method for quantifying the progress of a cell death event was developed and is presented here.

Multicompartmented microfluidic device for characterization of dose-dependent cadmium cytotoxicity in BALB/3T3 fibroblast cells.

This paper describes the development of a miniaturized multicompartmented microfluidic device for high-throughput cell cytotoxicity assays and its applicability to the investigation of cadmium-induced cytotoxicity. A steady gradient of cadmium was generated inside the compartments to study the effects of cadmium ion on BALB/3T3 fibroblast cells in a dose-dependent fashion. The device allowed the performance of multiplexed assays to probe the dosage effect of cadmium, morphological alterations of live cells, regulation of proliferation and viability of cells, determination of reactive oxygen species, mechanisms of cell death, i.

Generation of stable concentration gradients in 2D and 3D environments using a microfluidic ladder chamber.

We have developed a simple microfluidic device for generating stable concentration gradients in 2D and 3D environments. The device, termed the Ladder Chamber, uses a two-compartment diffusion system to generate steady state gradients across flow-free channels that connect the source and sink channels. To demonstrate the utility of the Ladder Chamber for cell migration, neutrophil chemotaxis was successfully observed in soluble chemoattractant (IL-8) gradient.

Microfluidic culture platform for neuroscience research.

This protocol describes the fabrication and use of a microfluidic device to culture central nervous system (CNS) and peripheral nervous system neurons for neuroscience applications. This method uses replica-molded transparent polymer parts to create miniature multi-compartment cell culture platforms. The compartments are made of tiny channels with dimensions of tens to hundreds of micrometers that are large enough to culture a few thousand cells in well-controlled microenvironments.

External force-assisted cell positioning inside microfluidic devices.

This paper describes straightforward approaches to positioning cells within microfluidic devices that can be implemented without special equipment or fabrication steps. External forces can effectively transport and position cells in preferred locations inside microfluidic channels. Except for centrifugal force-based positioning that can be used with any microfluidic channels, hydrodynamic and gravitational force-based positioning yield reproducible and biocompatible results when implemented with a microfluidic "module" that contains a barrier with embedded microgrooves.

Microfluidic chambers for cell migration and neuroscience research.

This chapter describes the fabrication and use microfluidic chambers for cell migration and neuroscience research. Both microfluidic chambers are made using soft lithography and replica molding. The main advantages of using soft lithography to create microfluidic chambers are reproducibility, ease of use, and straightforward fabrication procedures.

Quantitative analyses of shape-selective intercalation of isomeric mixtures of muconates into [LiAl2(OH)6]Cl.yH2O layered double hydroxide.

Quantitative investigation of the shape selectivity for the competitive intercalation reaction of isomeric mixtures in the interlayer of LDH was achieved by analyzing the solid phases synthesized by the reaction of [LiAl(2)(OH)(6)]Cl.yH(2)O with various compositional mixtures of (E,E)- and (Z,Z)-muconates. The apparent partition constant K' for the anion-exchange reaction between (E,E)- and (Z,Z)-muconates was quite dependent on the mole fraction of muconates in solution.

A microfluidic culture platform for CNS axonal injury, regeneration and transport.

Investigation of axonal biology in the central nervous system (CNS) is hindered by a lack of an appropriate in vitro method to probe axons independently from cell bodies. Here we describe a microfluidic culture platform that polarizes the growth of CNS axons into a fluidically isolated environment without the use of targeting neurotrophins. In addition to its compatibility with live cell imaging, the platform can be used to (i) isolate CNS axons without somata or dendrites, facilitating biochemical analyses of pure axonal fractions and (ii) localize physical and chemical treatments to axons or somata.

Human neural stem cell growth and differentiation in a gradient-generating microfluidic device.

This paper describes a gradient-generating microfluidic platform for optimizing proliferation and differentiation of neural stem cells (NSCs) in culture. Microfluidic technology has great potential to improve stem cell (SC) cultures, whose promise in cell-based therapies is limited by the inability to precisely control their behavior in culture. Compared to traditional culture tools, microfluidic platforms should provide much greater control over cell microenvironment and rapid optimization of media composition using relatively small numbers of cells.

Patterned cell culture inside microfluidic devices.

This paper describes a simple plasma-based dry etching method that enables patterned cell culture inside microfluidic devices by allowing patterning, fluidic bonding and sterilization steps to be carried out in a single step. This plasma-based dry etching method was used to pattern cell-adhesive and non-adhesive areas on the glass and polystyrene substrates. The patterned substrate was used for selective attachment and growth of human umbilical vein endothelial cells, MDA-MB-231 human breast cancer cells, NIH 3T3 mouse fibroblasts, and primary rat cortical neurons.

Generation of dynamic temporal and spatial concentration gradients using microfluidic devices.

This paper describes a microfluidic approach to generate dynamic temporal and spatial concentration gradients using a single microfluidic device. Compared to a previously described method that produced a single fixed gradient shape for each device, this approach combines a simple "mixer module" with gradient generating network to control and manipulate a number of different gradient shapes. The gradient profile is determined by the configuration of fluidic inputs as well as the design of microchannel network.

Orientation-controlled assembly and solvothermal ion-exchange of layered double hydroxide nanocrystals.

The orientation-controlled LDH crystals on Si substrates were intercalated by dicarboxylate ions to give the anisotropic layer expansion.

Microfluidic Multicompartment Device for Neuroscience Research.

This paper describes and characterizes a novel microfabricated neuronal culture device. This device combines microfabrication, microfluidic, and surface micropatterning techniques to create a multicompartment neuronal culturing device that can be used in a number of neuroscience research applications. The device is fabricated in poly(dimethylsiloxane), PDMS, using soft lithography techniques.