scholarly journals A surface acoustic wave-driven micropump for particle uptake investigation under physiological flow conditions in very small volumes

2015 ◽  
Vol 6 ◽  
pp. 414-419 ◽  
Author(s):  
Florian G Strobl ◽  
Dominik Breyer ◽  
Phillip Link ◽  
Adriano A Torrano ◽  
Christoph Bräuchle ◽  
...  

Static conditions represent an important shortcoming of many in vitro experiments on the cellular uptake of nanoparticles. Here, we present a versatile microfluidic device based on acoustic streaming induced by surface acoustic waves (SAWs). The device offers a convenient method for introducing fluid motion in standard cell culture chambers and for mimicking capillary blood flow. We show that shear rates over the whole physiological range in sample volumes as small as 200 μL can be achieved. A precise characterization method for the induced flow profile is presented and the influence of flow on the uptake of Pt-decorated CeO2 particles by endothelial cells (HMEC-1) is demonstrated. Under physiological flow conditions the particle uptake rates for this system are significantly lower than at low shear conditions. This underlines the vital importance of the fluidic environment for cellular uptake mechanisms.

2021 ◽  
Author(s):  
Marco Testaguzza ◽  
Mehdi Benhassine ◽  
Haroun Frid ◽  
Laurence Gebhart ◽  
Karim Zouaoui Boudjeltia ◽  
...  

Abstract Ischemic Stroke is the most frequent type of stroke and is subject to many studies investigating prevention means. Avoiding the difficulties and ethical problems of experimental in-vivo research, in-vitro testing is a convenient way of studying in controlled conditions the morphological impact and mechanical aspects of emboli dynamics. This in-vitro study was performed with two realistic silicone aortic-arch phantoms submitted to physiological pulsatile flow conditions. In the in-vitro test bed, using automatic image tracking and analysis, it was made possible detecting and tracking artificial spherical emboli candidates circulating in the anatomic aortic-arch models under a realistic based-patient blood flow profile. The emboli trajectories as well as their repartition in the different supra-aortic branches are presented for the two aortic-arch geometries obtained from CT scans. Through a statistical analysis performed with several artificial emboli sizes, the experimental study shows that the repartition percentages of the emboli closely follow the flowrate repartition percentages for both aortic-arch models, suggesting that higher flowrates lead to higher concentrations of emboli in a given artery. Sets of human thrombi were also injected and the repartition percentages have been established, giving the same trend as for artificial emboli.


2014 ◽  
Vol 112 (1) ◽  
pp. 43-48 ◽  
Author(s):  
Feng Guo ◽  
Peng Li ◽  
Jarrod B. French ◽  
Zhangming Mao ◽  
Hong Zhao ◽  
...  

The interactions between pairs of cells and within multicellular assemblies are critical to many biological processes such as intercellular communication, tissue and organ formation, immunological reactions, and cancer metastasis. The ability to precisely control the position of cells relative to one another and within larger cellular assemblies will enable the investigation and characterization of phenomena not currently accessible by conventional in vitro methods. We present a versatile surface acoustic wave technique that is capable of controlling the intercellular distance and spatial arrangement of cells with micrometer level resolution. This technique is, to our knowledge, among the first of its kind to marry high precision and high throughput into a single extremely versatile and wholly biocompatible technology. We demonstrated the capabilities of the system to precisely control intercellular distance, assemble cells with defined geometries, maintain cellular assemblies in suspension, and translate these suspended assemblies to adherent states, all in a contactless, biocompatible manner. As an example of the power of this system, this technology was used to quantitatively investigate the gap junctional intercellular communication in several homotypic and heterotypic populations by visualizing the transfer of fluorescent dye between cells.


2014 ◽  
Vol 136 (12) ◽  
Author(s):  
Sharan Ramaswamy ◽  
Steven M. Boronyak ◽  
Trung Le ◽  
Andrew Holmes ◽  
Fotis Sotiropoulos ◽  
...  

The ability to replicate physiological hemodynamic conditions during in vitro tissue development has been recognized as an important aspect in the development and in vitro assessment of engineered heart valve tissues. Moreover, we have demonstrated that studies aiming to understand mechanical conditioning require separation of the major heart valve deformation loading modes: flow, stretch, and flexure (FSF) (Sacks et al., 2009, "Bioengineering Challenges for Heart Valve Tissue Engineering," Annu. Rev. Biomed. Eng., 11(1), pp. 289–313). To achieve these goals in a novel bioreactor design, we utilized a cylindrical conduit configuration for the conditioning chamber to allow for higher fluid velocities, translating to higher shear stresses on the in situ tissue specimens while retaining laminar flow conditions. Moving boundary computational fluid dynamic (CFD) simulations were performed to predict the flow field under combined cyclic flexure and steady flow (cyclic-flex-flow) states using various combinations of flow rate, and media viscosity. The device was successfully constructed and tested for incubator housing, gas exchange, and sterility. In addition, we performed a pilot experiment using biodegradable polymer scaffolds seeded with bone marrow derived stem cells (BMSCs) at a seeding density of 5 × 106 cells/cm2. The constructs were subjected to combined cyclic flexure (1 Hz frequency) and steady flow (Re = 1376; flow rate of 1.06 l/min (LPM); shear stress in the range of 0–9 dynes/cm2) for 2 weeks to permit physiological shear stress conditions. Assays revealed significantly (P < 0.05) higher amounts of collagen (2051 ± 256 μg/g) at the end of 2 weeks in comparison to similar experiments previously conducted in our laboratory but performed at subphysiological levels of shear stress (<2 dynes/cm2; Engelmayr et al., 2006, "Cyclic Flexure and Laminar Flow Synergistically Accelerate Mesenchymal Stem Cell-Mediated Engineered Tissue Formation: Implications for Engineered Heart Valve Tissues," Biomaterials, 27(36), pp. 6083–6095). The implications of this novel design are that fully coupled or decoupled physiological flow, flexure, and stretch modes of engineered tissue conditioning investigations can be readily accomplished with the inclusion of this device in experimental protocols on engineered heart valve tissue formation.


Author(s):  
Sebastian Sachs ◽  
Christian Cierpka ◽  
Jörg König

The application of standing surface acoustic waves (sSAW) has enabled the development of many flexible and easily scalable concepts for the fractionation of particle solutions in the field of microfluidic lab-ona-chip devices. In this context, the acoustic radiation force (ARF) is often employed for the targeted manipulation of particle trajectories, whereas acoustically induced flows complicate efficient fractionation in many systems [Sehgal and Kirby (2017)]. Therefore, a characterization of the superimposed fluid motion is essential for the design of such devices. The present work focuses on a structural analysis of the acousticallyexcited flow, both in the center and in the outer regions of the standing wave field. For this, experimental flow measurements were conducted using astigmatism particle tracking velocimetry (APTV) [Cierpka et al. (2010)]. Through multiple approaches, we address the specific challenges for reliable velocity measurements in sSAW due to limited optical access, the influence of the ARF on particle motion, and regions of particle depletion caused by multiple pressure nodes along the channel width and height. Variations in frequency, channel geometry, and electrical power allow for conclusions to be drawn on the formation of a complex, three-dimensional vortex structure at the beginning and end of the sSAW.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
O King ◽  
D Cruz-Moreira ◽  
W Kit-Anan ◽  
A Sayed ◽  
B.X Wang ◽  
...  

Abstract   The myocardium is one of the most densely vascularised tissues in the body, with dynamic metabolic demand from beating cardiomyocytes (CM) necessitating an intimate relationship with microvasculature. Endothelial cells (EC) produce a diverse array of cardio-active factors which acutely and chronically modulate myocardial phenotype. Disruption of CM-EC signalling results in pathological remodelling, and ultimately organ failure. However, as physiologically relevant recapitulation of CM-EC interaction has been difficult to achieve in vitro, many molecular mechanisms governing their interaction remain poorly understood. To induce cardiac vasculogenesis in vitro, we have developed microfluidic chips which subject 3D hydrogel cultures to precisely controlled flow. We then co-cultured human cardiac microvascular ECs, human left ventricular fibroblasts (FB), and human induced pluripotent stem cell-derived cardiomyocytes for 5 days under a pro-vasculogenic protocol (0.5 ul/min flow rate, 50ng/ml VEGF, 100ng/ml Ang-1). Via live and fixed immunofluorescence microscopy, we observed spontaneous formation of a microvasculature network with a continuously open lumen embedded within beating myocardium. Simultaneous quantification of iPSC-CM contractility and perfused red blood cell velocity reveals biomimetic pulsatile flow profile within the microvasculature. To evaluate the influence of microvasculature on CM function, we incorporated CMs differentiated from stem cells with the genetically encoded calcium biosensor GCaMP6F. Compared to CM only control, vascularised preparations demonstrate significantly faster calcium transient time to peak (−11.5%, p=0.007) and time to 50% relaxation (−15%, p=0.01). Under static conditions and 1Hz electrical stimulation, presence of EC was associated with reduced iPSC-CM arrhythmia at baseline (p&lt;0.0001) and during 1uM isoprenaline treatment (p=0.0003), while maintaining isoprenaline induced Ca2+ handling quickening. To the best of our knowledge, this work represents the first fully perfusable model of the myocardial microvasculature, and highlights the importance of EC regulatory influence on CM function. Further work aims to investigate underlying molecular mechanisms to provide therapeutically relevant insight into cardiac biology. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): British Heart Foundation


2021 ◽  
Vol 12 ◽  
Author(s):  
Lanette Kempers ◽  
Evelien G. G. Sprenkeler ◽  
Abraham C. I. van Steen ◽  
Jaap D. van Buul ◽  
Taco W. Kuijpers

The actin-related protein (ARP) 2/3 complex, essential for organizing and nucleating branched actin filaments, is required for several cellular immune processes, including cell migration and granule exocytosis. Recently, genetic defects in ARPC1B, a subunit of this complex, were reported. Mutations in ARPC1B result in defective ARP2/3-dependent actin filament branching, leading to a combined immunodeficiency with severe inflammation. In vitro, neutrophils of these patients showed defects in actin polymerization and chemotaxis, whereas adhesion was not altered under static conditions. Here we show that under physiological flow conditions human ARPC1B-deficient neutrophils were able to transmigrate through TNF-α-pre-activated endothelial cells with a decreased efficiency and, once transmigrated, showed definite impairment in subendothelial crawling. Furthermore, severe locomotion and migration defects were observed in a 3D collagen matrix and a perfusable vessel-on-a-chip model. These data illustrate that neutrophils employ ARP2/3-independent steps of adhesion strengthening for transmigration but rely on ARP2/3-dependent modes of migration in a more complex multidimensional environment.


nano Online ◽  
2016 ◽  
Author(s):  
Florian Strobl ◽  
Dominik Breyer ◽  
Phillip Link ◽  
Adriano Torrano ◽  
Christoph Bräuchle ◽  
...  

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