Microfluidics

Novel microfluidic tools allow new ways to manufacture and test drug delivery systems. Organ-on-a-chip systems - microscale recapitulations of complex organ functions - promise to improve the drug development pipeline. This review highlights the importance of integrating microfluidic networks with 3D tissue engineered models to create organ-on-a-chip platforms, able to meet the demand of creating robust preclinical screening models. Specific examples are cited to demonstrate the use of these systems for studying the performance of drug delivery vectors and thereby reduce the discrepancies between their performance at preclinical and clinical trials. We also highlight the future directions that need to be pursued by the research community for these proof-of-concept studies to achieve the goal of accelerating clinical translation of drug delivery nanoparticles.

Novel microfluidic tools allow new ways to manufacture and test drug delivery systems. Organ-on-a-chip systems - microscale recapitulations of complex organ functions - promise to improve the drug development pipeline. This review highlights the importance of integrating microfluidic networks with 3D tissue engineered models to create organ-on-a-chip platforms, able to meet the demand of creating robust preclinical screening models. Specific examples are cited to demonstrate the use of these systems for studying the performance of drug delivery vectors and thereby reduce the discrepancies between their performance at preclinical and clinical trials. We also highlight the future directions that need to be pursued by the research community for these proof-of-concept studies to achieve the goal of accelerating clinical translation of drug delivery nanoparticles.

An increase in random molecular vibrations of a solid owing to heating above the melting point leads to a decrease in its long-range order and a loss of structural symmetry. Therefore conventional liquids are isotropic media. Here we report on a light-induced isothermal transition of a polymer film from an isotropic solid to an anisotropic liquid state in which the

Laminate construction of microfluidic devices offers a means to incorporate both additive and subtractive manufacturing techniques for the development of multiplexed fluidic devices that have, for example, porous membranes formed-in-place (FIP). Important applications for these hybrid devices includes sample preparation, separations, and containment of samples fed by a single inlet and outlet, such as multiple samples of suspended cells in culture contained in their respective wells. We describe the development and performance of a fluidic card for the NASA Ames GeneSat-1 program for autonomous cell culture experiments in space. The fluidic card was constructed as a multi-layer laminate of acrylic and bio-compatible bonding adhesive, using laser ablation to form the channels with porous membranes placed at the inlet and outlet of each sample well to contain individual samples of E. coli and prevent cross contamination.

The development of a bio-hybrid tactile sensor array that incorporates a skin analogue comprised of alginate encapsulated fibroblasts is described. The electrical properties are modulated by mechanical stress induced during contact, and changes are detected by a ten-channel dual-electrode impedance sensing array. By continuously monitoring the impedance of the sensor array at a fixed frequency, whilst normal and tangential loads are applied to the skin surface, transient mechanotransduction has been observed. The results demonstrate the effectiveness and feasibility of the preliminary prototype bio-hybrid tactile sensor.

Emerging therapies have begun to evaluate the abilities of Müller glial cells (MGCs) to protect and/or regenerate neurons following retina injury. The migration of donor cells is central to many reparative strategies, where cells must achieve appropriate positioning to facilitate localized repair. Although chemical cues have been implicated in the MGC migratory responses of numerous retinopathies, MGC-based therapies have yet to explore the extent to which external biochemical stimuli can direct MGC behavior. The current study uses a microfluidics-based assay to evaluate the migration of cultured rMC-1 cells (as model MGC) in response to quantitatively-controlled microenvironments of signaling factors implicated in retinal regeneration: basic Fibroblast Growth factor (bFGF or FGF2); Fibroblast Growth factor 8 (FGF8); Vascular Endothelial Growth Factor (VEGF); and Epidermal Growth Factor (EGF). Findings indicate that rMC-1 cells exhibited minimal motility in response to FGF2, FGF8 and VEGF, but highly-directional migration in response to EGF. Further, the responses were blocked by inhibitors of EGF-R and of the MAPK signaling pathway. Significantly, microfluidics data demonstrate that changes in the EGF gradient (i.e. change in EGF concentration over distance) resulted in the directional chemotactic migration of the cells. By contrast, small increases in EGF concentration, alone, resulted in non-directional cell motility, or chemokinesis. This microfluidics-enhanced approach, incorporating the ability both to modulate and asses the responses of motile donor cells to a range of potential chemotactic stimuli, can be applied to potential donor cell populations obtained directly from human specimens, and readily expanded to incorporate drug-eluting biomaterials and combinations of desired ligands.

The curvature dependence of the surface tension is related to the excess equimolar radius of liquid drops, i.e., the deviation of the equimolar radius from that defined with the macroscopic capillarity approximation. Based on the Tolman [J. Chem. Phys. 17, 333 (1949)] approach and its interpretation by Nijmeijer et al. [J. Chem. Phys. 96, 565 (1991)], the surface tension of spherical interfaces is analysed in terms of the pressure difference due to curvature. In the present study, the excess equimolar radius, which can be obtained directly from the density profile, is used instead of the Tolman length. Liquid drops of the truncated-shifted Lennard-Jones fluid are investigated by molecular dynamics simulation in the canonical ensemble, with equimolar radii ranging from 4 to 33 times the Lennard-Jones size parameter sigma. In these simulations, the magnitudes of the excess equimolar radius and the Tolman length are shown to be smaller than sigma/2. Other methodical approaches, from which mutually contradicting findings have been reported, are critically discussed, outlining possible sources of inaccuracy.

Lab on Chip technologies have enabled the possibility of novel μTAS devices (micro Total Analysis System) that could drastically improve health care services for billions of people around the world. However, serious drawbacks that reside in fluid handling technology currently available for these systems often restrict the commercialization of such devices. This work demonstrates a novel fluid handling method as a possible alternative to current micropumping techniques for disposable microfluidic chips. This technology is based on a single use, low cost, thermal micropumping system in which expandable microsphere mixtures are activated by commercial grade laser diodes to achieve flow rates as high as 2.2 μl/s and total volumes over 160 μl. With the addition of a volume dependent shut off valve, nanoliter repeatability is realized. Pressure and heat transfer related data are presented. Finally, the possible prospects and limitations of this technology as a core element in unified optofluidic systems are discussed.

CEK Microvalve
The main function of a microvalve is switching the direction of the flow at the desired time to control and regulate the fluid stream. Microvalves are one of the most important components of integrated lab-on-a-chip (LOC) devices. Using microvalves with high performance, the sequential loading and washing processes could be performed accurately and fast. However, the existing microvalves have lots of serious problems which are unsolved. Thus, a new design is highly required to develop practical and efficient microvalves and overcome the current problems. Such a microvalve could be a great step toward developing integrated LOC devices. In this entry a new ICEK microvalve using a heterogeneous particle is introduced. This ICEK microvalve is easily controlled by applying two perpendicular electric fields, stable and fast, has small dead volume and short response time, has no leakage, and is easy ...

It is currently impossible to control irrigation at the level of a single plant. Even with drip irrigation, in which emitters could conceivably be placed on a plant-by-plant basis, there is no way to control the amount of water emitted according to the needs of the individual plants. If such a capability were practically available on farms, the result would be a step change in precision agriculture, such that the water input for every plant in a farm (or field) could be optimized. Therefore, we are exploring the possibility of developing a microfluidic system that could be controlled, capillary by capillary, to deliver the needed amount of water to individual plants in a large field. The principal aim is to show proof of concept by building and testing a prototype to produce data suggestive of the potential for multiple individually controllable microfluidic ports along a pressurized tube of water. Hence, in this study we perform experiments using a thermally actuated microvalve for...

Soft robots possess many attributes that are difficult, if not impossible, to achieve with conventional robots composed of rigid materials. Yet, despite recent advances, soft robots must still be tethered to hard robotic control systems and power sources. New strategies for creating completely soft robots, including soft analogues of these crucial components, are needed to realize their full potential. Here we report the untethered operation of a robot composed solely of soft materials. The robot is controlled with microfluidic logic that autonomously regulates fluid flow and, hence, catalytic decomposition of an on-board monopropellant fuel supply. Gas generated from the fuel decomposition inflates fluidic networks downstream of the reaction sites, resulting in actuation. The body and microfluidic logic of the robot are fabricated using moulding and soft lithography, respectively, and the pneumatic actuator networks, on-board fuel reservoirs and catalytic reaction chambers needed f...

An integrated micro/nano-fluidic system is presented for protein analysis. It is comprised of an integrated micromixer (IMM) and a preconcentrator with a separation column. The passive and planar type of IMM is based on an unbalanced split and the cross collision of the fluidic streams. The IMM can be easily fabricated and integrated to the microfluidic system. The preconcentrator has nanochannels formed by the electrical breakdown of polydimethylsiloxane (PDMS) membrane by applying a high electrical shock, but without any nano-lithography. The integrated microdevice was used for sample preparation (mixing with tagging molecules) and subsequent concentration of proteins. Proteins were electrokinetically trapped near the junction of the micro/nanochannels. We show a conceptual design and a simple microfluidic system for purposes of mixing and preconcentration. Figure Mixing and preconcentration of dissolved proteins using an integrated micro/nano-fluidic system

Recent applications in tissue engineering and regenerative medicine have highlighted the utility of microfluidic fiber fabrication. On page 11 M. A. Daniele and team show how this process uses microflow shaping to generate a core-sheath profile, which can be subsequently solidified into microfibers of various shapes and chemistries, providing the capability to incorporate and organize both fragile biomolecules and cell-cultures within individual fibers and bioactive textiles.

Spatial confinement in nanoporous media affects the structure, thermodynamics and mobility of molecular soft matter often markedly. This article reviews thermodynamic equilibrium phenomena, such as physisorption, capillary condensation, crystallisation, self-diffusion, and structural phase transitions as well as selected aspects of the emerging field of spatially confined, non-equilibrium physics, i.e. the rheology of liquids, capillarity-driven flow phenomena, and imbibition front broadening in nanoporous materials. The observations in the nanoscale systems are related to the corresponding bulk phenomenologies. The complexity of the confined molecular species is varied from simple building blocks, like noble gas atoms, normal alkanes and alcohols to liquid crystals, polymers, ionic liquids, proteins and water. Mostly, experiments with mesoporous solids of alumina, gold, carbon, silica, and silicon with pore diameters ranging from a few up to 50 nm are presented. The observed peculiarities of nanopore-confined condensed matter are also discussed with regard to applications.
A particular emphasis is put on texture formation upon crystallisation in nanoporous media, a topic both of high fundamental interest and of increasing nanotechnological importance, e.g. for the synthesis of organic/inorganic hybrid materials by melt infiltration, the usage of nanoporous solids in crystal nucleation or in template-assisted electrochemical deposition of nano structures.

Breast and prostate cancers preferentially metastasise to bone tissue, with metastatic lesions
forming in the skeletons of most patients. On arriving in bone tissue, disseminated tumour cells
enter a mechanical microenvironment that is substantially different to that of the primary tumour
and is largely regulated by bone cells. Osteocytes, the most ubiquitous bone cell type, orchestrate
healthy bone remodelling in response to physical exercise. However, the effects of mechanical
loading of osteocytes on cancer cell behaviour is still poorly understood. The aim of this study
was to characterise the effects of osteocyte mechanical stimulation on the behaviour of breast and
prostate cancer cells. To replicate an osteocyte-controlled environment, this study treated breast
(MDA-MB-231 and MCF-7) and prostate (PC-3 and LNCaP) cancer cell lines with conditioned media
from MLO-Y4 osteocyte-like cells exposed to mechanical stimulation in the form of fluid shear stress.
We found that osteocyte paracrine signalling acted to inhibit metastatic breast and prostate tumour
growth, characterised by reduced proliferation and invasion and increased migration. In breast
cancer cells, these effects were largely reversed by mechanical stimulation of osteocytes. In contrast,
conditioned media from mechanically stimulated osteocytes had no effect on prostate cancer cells.
To further investigate these interactions, we developed a microfluidic organ-chip model using the
Emulate platform. This new organ-chip model enabled analysis of cancer cell migration, proliferation
and invasion in the presence of mechanical stimulation of osteocytes by fluid shear stress, resulting
in increased invasion of breast and prostate cancer cells. These findings demonstrate the importance
of osteocytes and mechanical loading in regulating cancer cell behaviour and the need to incorporate
these factors into predictive in vitro models of bone metastasis.