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Yusuf B Arık, Marinke W van der Helm, Mathieu Odijk, Loes I Segerink, Robert Passier, Albert van den Berg, Andries D van der Meer
Disruption of tissue barriers formed by cells is an integral part of the pathophysiology of many diseases. Therefore, a thorough understanding of tissue barrier function is essential when studying the causes and mechanisms of disease as well as when developing novel treatments. In vitro methods play an integral role in understanding tissue barrier function, and several techniques have been developed in order to evaluate barrier integrity of cultured cell layers, from microscopy imaging of cell-cell adhesion proteins to measuring ionic currents, to flux of water or transport of molecules across cellular barriers...
July 2018: Biomicrofluidics
Mario Gutierrez, Lauro Sebastian Ojeda, Omolola Eniola-Adefeso
The field of drug delivery has taken an interest in combating numerous blood and heart diseases via the use of injectable vascular-targeted carriers (VTCs). However, VTC technology has encountered limited efficacy due to a variety of challenges associated with the immense complexity of the in vivo blood flow environment, including the hemodynamic interactions of blood cells, which impact their margination and adhesion to the vascular wall. Red blood cell (RBC) physiology, i.e., size, shape, and deformability, drive cellular distribution in blood flow and has been shown to impact VTC margination to the vessel wall significantly...
July 2018: Biomicrofluidics
Barbara Bachmann, Sarah Spitz, Mario Rothbauer, Christian Jordan, Michaela Purtscher, Helene Zirath, Patrick Schuller, Christoph Eilenberger, Syed Faheem Ali, Severin Mühleder, Eleni Priglinger, Michael Harasek, Heinz Redl, Wolfgang Holnthoner, Peter Ertl
Reengineering functional vascular networks in vitro remains an integral part in tissue engineering, since the incorporation of non-perfused tissues results in restricted nutrient supply and limited waste removal. Microfluidic devices are routinely used to mimic both physiological and pathological vascular microenvironments. Current procedures either involve the investigation of growth factor gradients and interstitial flow on endothelial cell sprouting alone or on the heterotypic cell-cell interactions between endothelial and mural cells...
July 2018: Biomicrofluidics
Taylor J Thompson, Bumsoo Han
Metastasis is the ultimate cause of death among the vast majority of cancer patients. This process is comprised of multiple steps, including the migration of circulating cancer cells across microvasculature. This trans-endothelial migration involves the adhesion and eventual penetration of cancer cells to the vasculature of the target organ. Many of these mechanisms remain poorly understood due to poor control of pathophysiological conditions in tumor models. In this work, a microfluidic device was developed to support the culture and observation of engineered microvasculature with systematic control of the environmental characteristics...
July 2018: Biomicrofluidics
M Herbig, A Mietke, P Müller, O Otto
Real-time deformability (RT-DC) is a method for high-throughput mechanical and morphological phenotyping of cells in suspension. While analysis rates exceeding 1000 cells per second allow for a label-free characterization of complex biological samples, e.g., whole blood, data evaluation has so far been limited to a few geometrical and material parameters such as cell size, deformation, and elastic Young's modulus. But as a microscopy-based technology, RT-DC actually generates and yields multidimensional datasets that require automated and unbiased tools to obtain morphological and rheological cell information...
July 2018: Biomicrofluidics
Cynthia Hajal, Marco Campisi, Clara Mattu, Valeria Chiono, Roger D Kamm
The blood-brain barrier (BBB) is the tightest endothelial barrier in humans. Characterized by the presence of tight endothelial junctions and adherens junctions, the primary function of the BBB is to maintain brain homeostasis through the control of solute transit across the barrier. The specific features of this barrier make for unique modes of transport of solutes, nanoparticles, and cells across the BBB. Understanding the different routes of traffic adopted by each of these is therefore critical in the development of targeted therapies...
July 2018: Biomicrofluidics
D Huber, G V Kaigala
This paper describes a micro fluorescence in situ hybridization ( μ FISH)-based rapid detection of cytogenetic biomarkers on formalin-fixed paraffin embedded (FFPE) tissue sections. We demonstrated this method in the context of detecting human epidermal growth factor 2 (HER2) in breast tissue sections. This method uses a non-contact microfluidic scanning probe (MFP), which localizes FISH probes at the micrometer length-scale to selected cells of the tissue section. The scanning ability of the MFP allows for a versatile implementation of FISH on tissue sections...
July 2018: Biomicrofluidics
Joseph W Song, Jungwook Paek, Kyu-Tae Park, Jeongyun Seo, Dongeun Huh
Occlusion of distal airways due to mucus plugs is a key pathological feature common to a wide variety of obstructive pulmonary diseases. Breathing-induced movement of airway mucus plugs along the respiratory tract has been shown to generate abnormally large mechanical stresses, acting as an insult that can incite acute injury to the airway epithelium. Here, we describe a unique microengineering strategy to model this pathophysiological process using a bioinspired microfluidic device. Our system combines an air-liquid interface culture of primary human small airway epithelial cells with a microengineered biomimetic platform to replicate the process of mucus exudation induced by airway constriction that leads to the formation of mucus plugs across the airway lumen...
July 2018: Biomicrofluidics
Michael T Griffin, Yuanzheng Zhu, Zixiang Liu, Cyrus K Aidun, David N Ku
Platelet accumulation under high shear rates at the site of atherosclerotic plaque rupture leads to myocardial infarction and stroke. Current antiplatelet therapies remain ineffective within a large percentage of the population, while presenting significant risks for bleeding. We explore a novel way to inhibit arterial thrombus formation by biophysical means without the use of platelet inactivating drugs. Our computational multi-scale dynamics model has predicted that charged particles of a specific size may entangle von Willebrand Factor (vWF) polymers and reduce the amount of elongation at high shear rates...
July 2018: Biomicrofluidics
Janna Tenenbaum-Katan, Arbel Artzy-Schnirman, Rami Fishler, Netanel Korin, Josué Sznitman
The entire luminal surface of the lungs is populated with a complex yet confluent, uninterrupted airway epithelium in conjunction with an extracellular liquid lining layer that creates the air-liquid interface (ALI), a critical feature of healthy lungs. Motivated by lung disease modelling, cytotoxicity studies, and drug delivery assessments amongst other, in vitro setups have been traditionally conducted using macroscopic cultures of isolated airway cells under submerged conditions or instead using transwell inserts with permeable membranes to model the ALI architecture...
July 2018: Biomicrofluidics
Annalisa Dimasi, Yana Roka-Moiia, Filippo Consolo, Marco Rasponi, Gianfranco B Fiore, Marvin J Slepian, Alberto Redaelli
A microfluidic flow-based platform (μFP), able to stimulate platelets via exposure of shear stress patterns pertinent to cardiovascular devices and prostheses, was compared to the Hemodynamic Shearing Device (HSD)-a state-of-the-art bench-top system for exposure of platelets to defined levels and patterns of shear. Platelets were exposed to time-varying shear stress patterns in the two systems; in detail, platelets were recirculated in the μFP or stimulated in the HSD to replicate comparable exposure time...
July 2018: Biomicrofluidics
Olivier T Guenat, François Berthiaume
In the last decade, the advent of microfabrication and microfluidics and an increased interest in cellular mechanobiology have triggered the development of novel microfluidic-based platforms. They aim to incorporate the mechanical strain environment that acts upon tissues and in-vivo barriers of the human body. This article reviews those platforms, highlighting the different strains applied, and the actuation mechanisms and provides representative applications. A focus is placed on the skin and the lung barriers as examples, with a section that discusses the signaling pathways involved in the epithelium and the connective tissues...
July 2018: Biomicrofluidics
Salman Sohrabi, Jifu Tan, Doruk Erdem Yunus, Ran He, Yaling Liu
Isolating cells of interest from a heterogeneous population has been of critical importance in biological studies and clinical applications. In this study, a novel approach is proposed for utilizing an active ciliary system in microfluidic devices to separate particles based on their physical properties. In this approach, the bottom of the microchannel is covered with an equally spaced cilia array of various patterns which is actuated by an external stimuli. 3D simulations are carried out to study cilia-particle interaction and isolation dynamic in a microfluidic channel...
July 2018: Biomicrofluidics
Hilaria Mollica, Alessandro Coclite, Marco E Miali, Rui C Pereira, Laura Paleari, Chiara Manneschi, Andrea DeCensi, Paolo Decuzzi
Vascular adhesion of circulating tumor cells (CTCs) is a key step in cancer spreading. If inflammation is recognized to favor the formation of vascular "metastatic niches," little is known about the contribution of blood rheology to CTC deposition. Herein, a microfluidic chip, covered by a confluent monolayer of endothelial cells, is used for analyzing the adhesion and rolling of colorectal (HCT-15) and breast (MDA-MB-231) cancer cells under different biophysical conditions. These include the analysis of cell transport in a physiological solution and whole blood over a healthy and a TNF-α inflamed endothelium with a flow rate of 50 and 100 nl/min...
July 2018: Biomicrofluidics
Emi Sano, Chihiro Mori, Yuji Nashimoto, Ryuji Yokokawa, Hidetoshi Kotera, Yu-Suke Torisawa
Current in vitro 3D culture models lack a vascular system to transport oxygen and nutrients, as well as cells, which is essential to maintain cellular viability and functions. Here, we describe a microfluidic method to generate a perfusable vascular network that can form inside 3D multicellular spheroids and functionally connect to microchannels. Multicellular spheroids containing endothelial cells and lung fibroblasts were embedded within a hydrogel inside a microchannel, and then, endothelial cells were seeded into both sides of the hydrogel so that angiogenic sprouts from the cell spheroids and the microchannels were anastomosed to form a 3D vascular network...
July 2018: Biomicrofluidics
Robert G Mannino, Yongzhi Qiu, Wilbur A Lam
Numerous conditions and disease states such as sickle cell disease, malaria, thrombotic microangiopathy, and stroke significantly impact the microvasculature function and its role in disease progression. Understanding the role of cellular interactions and microvascular hemodynamic forces in the context of disease is crucial to understanding disease pathophysiology. In vivo models of microvascular disease using animal models often coupled with intravital microscopy have long been utilized to investigate microvascular phenomena...
July 2018: Biomicrofluidics
Daniel M Lewis, Nicholas Mavrogiannis, Zachary Gagnon, Sharon Gerecht
Electric cell-substrate impedance sensing (ECIS) is a quickly advancing field to measure the barrier function of endothelial cells. Most ECIS systems that are commercially available use gold electrodes, which are opaque and do not allow for real-time imaging of cellular responses. In addition, most ECIS systems have a traditional tissue culture Petri-dish set up. This conventional set-up does not allow the introduction of physiologically relevant shear stress, which is crucial for the endothelial cell barrier function...
July 2018: Biomicrofluidics
Bradley A Herbig, Xinren Yu, Scott L Diamond
Extreme flows can exist within pathological vessel geometries or mechanical assist devices which create complex forces and lead to thrombogenic problems associated with disease. Turbulence and boundary layer separation are difficult to obtain in microfluidics due to the low Reynolds number flow in small channels. However, elongational flows, extreme shear rates and stresses, and stagnation point flows are possible using microfluidics and small perfusion volumes. In this review, a series of microfluidic devices used to study pathological blood flows are described...
July 2018: Biomicrofluidics
Kiran Raj M, Jeevanjyoti Chakraborty, Sunando DasGupta, Suman Chakraborty
In this work, we have fabricated physiologically relevant polydimethylsiloxane microfluidic phantoms to investigate the fluid-structure interaction that arises from the interaction between a non-Newtonian fluid and the deformable wall. A shear thinning fluid (Xanthan gum solution) is used as the blood analog fluid. We have systematically analyzed the steady flow characteristics of the microfluidic phantom using pressure drop, deformation, and flow visualization using micro-PIV (Particle Image Velocimetry) to identify the intricate aspects of the pressure as well as the velocity field...
May 2018: Biomicrofluidics
D Ödman, E Werner, K D Dorfman, C R Doering, B Mehlig
In genome mapping experiments, long DNA molecules are stretched by confining them to very narrow channels, so that the locations of sequence-specific fluorescent labels along the channel axis provide large-scale genomic information. It is difficult, however, to make the channels narrow enough so that the DNA molecule is fully stretched. In practice, its conformations may form hairpins that change the spacings between internal segments of the DNA molecule, and thus the label locations along the channel axis...
May 2018: Biomicrofluidics
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