Assembly of a Three-Dimensional Multitype Bronchiole Coculture Model Using Magnetic Levitation

A longstanding goal in biomedical research has been to create organotypic cocultures that faithfully represent native tissue environments. There is presently great interest in representative culture models of the lung, which is a particularly challenging tissue to recreate in vitro. This study used magnetic levitation in conjunction with magnetic nanoparticles as a means of creating an organized three-dimensional (3D) coculture of the bronchiole that sequentially layers cells in a manner similar to native tissue architecture. The 3D coculture model was assembled from four human cell types in the bronchiole: endothelial cells, smooth muscle cells (SMCs), fibroblasts, and epithelial cells (EpiCs). This study represents the first effort to combine these particular cell types into an organized bronchiole coculture. These cell layers were first cultured in 3D by magnetic levitation, and then manipulated into contact with a custom-made magnetic pen, and again cultured for 48 h. Hematoxylin and eosin staining of the resulting coculture showed four distinct layers within the 3D coculture. Immunohistochemistry confirmed the phenotype of each of the four cell types and showed organized extracellular matrix formation, particularly, with collagen type I. Positive stains for CD31, von Willebrand factor, smooth muscle a-actin, vimentin, and fibronectin demonstrate the maintenance of the phenotype for endothelial cells, SMCs, and fibroblasts. Positive stains for mucin-5AC, cytokeratin, and E-cadherin after 7 days with and without 1% fetal bovine serum showed that EpiCs maintained the phenotype and function. This study validates magnetic levitation as a method for the rapid creation of organized 3D cocultures that maintain the phenotype and induce extracellular matrix formation

Spintromechanics of a Magnetic Nanoshuttle

We investigate theoretically the prospects for using a magnetic nanoelectromechanical single-electron tunneling (NEM-SET) device as an electronic spin filter. We find that strong magnetic exchange forces on the net spin of the mobile central dot of the NEM-SET structure lead to spin-dependent mechanical displacements ("spin polarons"), which give rise to vastly different tunnelling probabilities for electrons of different spin. The resulting spin polarization of the current can be controlled by bias and gate voltages and be very close to 100% at voltages and temperatures below a characteristic correlation energy set by the sum of the polaronic and Coulomb blockade energies.Comment: Accepted for publication as a Rapid Communication in Phys. Rev. B and selected as an "Editors' Suggestion" paper. This version has minor modifications compared to arXiv:1205.2979, which it replace

A spheroid toxicity assay using magnetic 3D bioprinting and real-time mobile device-based imaging

An ongoing challenge in biomedical research is the search for simple, yet robust assays using 3D cell cultures for toxicity screening. This study addresses that challenge with a novel spheroid assay, wherein spheroids, formed by magnetic 3D bioprinting, contract immediately as cells rearrange and compact the spheroid in relation to viability and cytoskeletal organization. Thus, spheroid size can be used as a simple metric for toxicity. The goal of this study was to validate spheroid contraction as a cytotoxic endpoint using 3T3 fibroblasts in response to 5 toxic compounds (all-trans retinoic acid, dexamethasone, doxorubicin, 5′-fluorouracil, forskolin), sodium dodecyl sulfate (+control), and penicillin-G (−control). Real-time imaging was performed with a mobile device to increase throughput and efficiency. All compounds but penicillin-G significantly slowed contraction in a dose-dependent manner (Z’ = 0.88). Cells in 3D were more resistant to toxicity than cells in 2D, whose toxicity was measured by the MTT assay. Fluorescent staining and gene expression profiling of spheroids confirmed these findings. The results of this study validate spheroid contraction within this assay as an easy, biologically relevant endpoint for high-throughput compound screening in representative 3D environments

Biospectroscopy of Nanodiamond-Induced Alterations in Conformation of Intra- and Extracellular Proteins: A Nanoscale IR Study

The toxicity of nanomaterials raises major concerns because of the impact that nanomaterials may have on health, which remains poorly understood. We need to explore the fate of individual nanoparticles in cells at nano and molecular levels to establish their safety. Conformational changes in secondary protein structures are one of the main indicators of impaired biological function and hence, the ability to identify these changes at a nanoscale level offers unique insights into the nanotoxicity of materials. Here, we used nanoscale infrared spectroscopy and demonstrated for the first time that nanodiamonds induced alterations in both extra- and intracellular secondary protein structures, leading to the formation of antiparallel β-sheet, β-turns, intermolecular β- sheet and aggregation of proteins. These conformational changes of the protein structure may result in the loss of functionality of proteins and in turn lead to adverse effects

The consequences of dependence between the formal area efficiency and the macroscopic electric field on linearity behavior in Fowler-Nordheim plots

This work presents a theoretical explanation for a crossover in the linear behavior in Fowler-Nordheim (FN) plots based on cold field electron emission (CFE) experimental data. It is characterized by a clear change in the decay rate of usually single-slope FN plots, and has been reported when non-uniform nano-emitters are subject to high macroscopic electric field $F_M$. We assume that the number of emitting spots, which defines an apparent formal area efficiency of CFE surfaces, depends on the macroscopic electric field. Non-uniformity is described by local enhancement factors $\left\{\gamma_j\right\}$, which are randomly assigned to each distinct emitter of a conducting CFE surface, from a discrete probability distribution $\rho{(\gamma_{j})}$, with $j=1,2$. It is assumed that $\rho{(\gamma_{1})} < \rho{(\gamma_{2})}$, and that $\gamma_{1} > \gamma_{2}$. The local current density is evaluated by considering a usual Schottky-Nordheim barrier. The results reproduce the two distinct slope regimes in FN plots when $F_M \in$ $[2,20]$ V/$\mu$m and are analyzed by taking into account the apparent formal area efficiency, the distribution $\rho$, and the slopes in the corresponding FN plot. Finally, we remark that our results from numerical solution of Laplace's equation, for an array of conducting nano-emitters with uniform apex radii $50$ nm but different local height, supports our theoretical assumptions and could used in orthodox CFE experiments to test our predictions

DNA Hybridization Sensors Based on Electrochemical Impedance Spectroscopy as a Detection Tool

Recent advances in label free DNA hybridization sensors employing electrochemical impedance spectroscopy ( EIS) as a detection tool are reviewed. These sensors are based on the modulation of the blocking ability of an electrode modified with a probe DNA by an analyte, i.e., target DNA. The probe DNA is immobilized on a self-assembled monolayer, a conducting polymer film, or a layer of nanostructures on the electrode such that desired probe DNA would selectively hybridize with target DNA. The rate of charge transfer from the electrode thus modified to a redox indicator, e. g., [Fe(CN)(6)](3-/4-), which is measured by EIS in the form of charge transfer resistance (R(ct)), is modulated by whether or not, as well as how much, the intended target DNA is selectively hybridized. Efforts made to enhance the selectivity as well as the sensitivity of DNA sensors and to reduce the EIS measurement time are briefly described along with brief future perspectives in developing DNA sensors.open484

Peptide-based targeting strategies for simultaneous imaging and therapy with nanovectors

Over recent years, multifunctional compounds that combine diagnostic and therapeutic modalities using one unified material have been developed and designated as theranostics. These compounds provide the chance to develop individually designed therapies against various diseases to accomplish personalized medicine. In this review, theranostic agents based on nanovectors (liposomes, naposomes, micelles, polymeric micelles and micelles built around a solid core) externally modified with targeting peptides able to simultaneously carry a drug and a contrast agent are described, demonstrating that peptide-modified nanovectors can selectively carry a drug to target cells with an imaging probe co-incorporated into the nanovector to monitor therapy

Synthetic micro/nanomotors in drug delivery

Nanomachines offer considerable promise for the treatment of diseases. The ability of man-made nanomotors to rapidly deliver therapeutic payloads to their target destination represents a novel nanomedicine approach. Synthetic nanomotors, based on a multitude of propulsion mechanisms, have been developed over the past decade toward diverse biomedical applications. In this review article, we journey from the use of chemically powered drug-delivery nanovehicles to externally actuated (fuel-free) drug-delivery nanomachine platforms, and conclude with future prospects and challenges for such practical propelling drug-delivery systems. As future micro/nanomachines become more powerful and functional, these tiny devices are expected to perform more demanding biomedical tasks and benefit different drug delivery applications

Virtual Reality as Tool for Bioprinting Quality Inspection: A Proof of Principle

As virtual reality (VR) has drastically evolved over the past few years, the field of applications of VR flourished way beyond the gaming industry. While commercial VR solutions might be available, there is a need to develop a workflow for specific applications. Bioprinting represents such an example. Here, complex 3D data is generated and needs to be visualized in the context of quality control. We demonstrate that the transfer to a commercially available VR software is possible by introducing an optimized workflow. In the present work, we developed a workflow for the visualization of the critical quality attribute (cQA) cell distribution in bioprinted (extrusion-based) samples in VR. The cQA cell distribution is directly influenced by the pre-processing step mixing of cell material in the bioink. Magnetic Resonance Imaging (MRI) was used as an analytical tool to generate spatially resolved 2.5 and 3D data of the bioprinted objects. A sample with poor quality in respect of the cQA cell distribution was identified as its inhomogeneous cell distribution could be displayed spatially resolved in VR. The described workflow facilitates the usage of VR as a tool for quality inspection in the field of bioprinting and represents a powerful tool for visualization of complex 3D MRI data