Modulated nanowire scaffold for highly efficient differentiation of mesenchymal stem cells.

BACKGROUND: Nanotopographical cues play a critical role as drivers of mesenchymal stem cell differentiation. Nanowire scaffolds, in this regard, provide unique and adaptable nanostructured surfaces with focal points for adhesion and with elastic properties determined by nanowire stiffness. RESULTS: We show that a scaffold of nanowires, which are remotely actuated by a magnetic field, mechanically stimulates mesenchymal stem cells. Osteopontin, a marker of osteogenesis onset, was expressed after cells were cultured for 1 week on top of the scaffold. Applying a magnetic field significantly boosted differentiation due to mechanical stimulation of the cells by the active deflection of the nanowire tips. The onset of differentiation was reduced to 2 days of culture based on the upregulation of several osteogenesis markers. Moreover, this was observed in the absence of any external differentiation factors. CONCLUSIONS: The magneto-mechanically modulated nanosurface enhanced the osteogenic differentiation capabilities of mesenchymal stem cells, and it provides a customizable tool for stem cell research and tissue engineering.

Magnetic core-shell nanowires as MRI contrast agents for cell tracking.

BACKGROUND: Identifying the precise location of cells and their migration dynamics is of utmost importance for achieving the therapeutic potential of cells after implantation into a host. Magnetic resonance imaging is a suitable, non-invasive technique for cell monitoring when used in combination with contrast agents. RESULTS: This work shows that nanowires with an iron core and an iron oxide shell are excellent materials for this application, due to their customizable magnetic properties and biocompatibility. The longitudinal and transverse magnetic relaxivities of the core-shell nanowires were evaluated at 1.5 T, revealing a high performance as T2 contrast agents. Different levels of oxidation and various surface coatings were tested at 7 T. Their effects on the T2 contrast were reflected in the tailored transverse relaxivities. Finally, the detection of nanowire-labeled breast cancer cells was demonstrated in T2-weighted images of cells implanted in both, in vitro in tissue-mimicking phantoms and in vivo in mouse brain. Labeling the cells with a nanowire concentration of 0.8 µg of Fe/mL allowed the detection of 25 cells/µL in vitro, diminishing the possibility of side effects. This performance enabled an efficient labelling for high-resolution cell detection after in vivo implantation (~ 10 nanowire-labeled cells) over a minimum of 40 days. CONCLUSIONS: Iron-iron oxide core-shell nanowires enabled the efficient and longitudinal cellular detection through magnetic resonance imaging acting as T2 contrast agents. Combined with the possibility of magnetic guidance as well as triggering of cellular responses, for instance by the recently discovered strong photothermal response, opens the door to new horizons in cell therapy and make iron-iron oxide core-shell nanowires a promising theranostic platform.

Magnon Mode Selective Spin Transport in Compensated Ferrimagnets.

We investigate the generation of magnonic thermal spin currents and their mode selective spin transport across interfaces in insulating, compensated ferrimagnet/normal metal bilayer systems. The spin Seebeck effect signal exhibits a nonmonotonic temperature dependence with two sign changes of the detected voltage signals. Using different ferrimagnetic garnets, we demonstrate the universality of the observed complex temperature dependence of the spin Seebeck effect. To understand its origin, we systematically vary the interface between the ferrimagnetic garnet and the metallic layer, and by using different metal layers we establish that interface effects play a dominating role. They do not only modify the magnitude of the spin Seebeck effect signal but in particular also alter its temperature dependence. By varying the temperature, we can select the dominating magnon mode and we analyze our results to reveal the mode selective interface transmission probabilities for different magnon modes and interfaces. The comparison of selected systems reveals semiquantitative details of the interfacial coupling depending on the materials involved, supported by the obtained field dependence of the signal.

Corrigendum: Mesenchymal stem cells cultured on magnetic nanowire substrates (2017 Nanotechnology 28 055703).

Stem cells have been shown to respond to extracellular mechanical stimuli by regulating their fate through the activation of specific signaling pathways. In this work, an array of iron nanowires (NWs) aligned perpendicularly to the surface was fabricated by pulsed electrodepositon in porous alumina templates followed by a partial removal of the alumina to reveal 2-3 µm of the NWs. This resulted in alumina substrates with densely arranged NWs of 33 nm in diameter separated by 100 nm. The substrates were characterized by scanning electron microscopy (SEM) energy dispersive x-ray analysis and vibrating sample magnetometer. The NW array was then used as a platform for the culture of human mesenchymal stem cells (hMSCs). The cells were stained for the cell nucleus and actin filaments, as well as immuno- stained for the focal adhesion protein vinculin, and then observed by fluorescence microscopy in order to characterize their spreading behavior. Calcein AM/ethidium homodimer-1 staining allowed the determination of cell viability. The interface between the cells and the NWs was studied using SEM. Results showed that hMSCs underwent a re-organization of actin filaments that translated into a change from an elongated to a spherical cell shape. Actin filaments and vinculin accumulated in bundles, suggesting the attachment and formation of focal adhesion points of the cells on the NWs. Though the overall number of cells attached on the NWs was lower compared to the control, the attached cells maintained a high viability (>90%) for up to 6 d. Analysis of the interface between the NWs and the cells confirmed the re-organization of F-actin and revealed the adhesion points of the cells on the NWs. Additionally, a net of filopodia surrounded each cell, suggesting the probing of the array to find additional adhesion points. The cells maintained their round shape for up to 6 d of culture. Overall, the NW array is a promising nanostructured platform for studying and influencing hMSCs differentiation.

Mesenchymal stem cells cultured on magnetic nanowire substrates.

Stem cells have been shown to respond to extracellular mechanical stimuli by regulating their fate through the activation of specific signaling pathways. In this work, an array of iron nanowires (NWs) aligned perpendicularly to the surface was fabricated by pulsed electrodepositon in porous alumina templates followed by a partial removal of the alumina to reveal 2-3 µm of the NWs. This resulted in alumina substrates with densely arranged NWs of 33 nm in diameter separated by 100 nm. The substrates were characterized by scanning electron microscopy (SEM) energy dispersive x-ray analysis and vibrating sample magnetometer. The NW array was then used as a platform for the culture of human mesenchymal stem cells (hMSCs). The cells were stained for the cell nucleus and actin filaments, as well as immuno-stained for the focal adhesion protein vinculin, and then observed by fluorescence microscopy in order to characterize their spreading behavior. Calcein AM/ethidium homodimer-1 staining allowed the determination of cell viability. The interface between the cells and the NWs was studied using SEM. Results showed that hMSCs underwent a re-organization of actin filaments that translated into a change from an elongated to a spherical cell shape. Actin filaments and vinculin accumulated in bundles, suggesting the attachment and formation of focal adhesion points of the cells on the NWs. Though the overall number of cells attached on the NWs was lower compared to the control, the attached cells maintained a high viability (>90%) for up to 6 d. Analysis of the interface between the NWs and the cells confirmed the re-organization of F-actin and revealed the adhesion points of the cells on the NWs. Additionally, a net of filopodia surrounded each cell, suggesting the probing of the array to find additional adhesion points. The cells maintained their round shape for up to 6 d of culture. Overall, the NW array is a promising nanostructured platform for studying and influencing hMSCs differentiation.

Semi-automated quantification of living cells with internalized nanostructures.

BACKGROUND: Nanostructures fabricated by different methods have become increasingly important for various applications in biology and medicine, such as agents for medical imaging or cancer therapy. In order to understand their interaction with living cells and their internalization kinetics, several attempts have been made in tagging them. Although methods have been developed to measure the number of nanostructures internalized by the cells, there are only few approaches aimed to measure the number of cells that internalize the nanostructures, and they are usually limited to fixed-cell studies. Flow cytometry can be used for live-cell assays on large populations of cells, however it is a single time point measurement, and does not include any information about cell morphology. To date many of the observations made on internalization events are limited to few time points and cells. RESULTS: In this study, we present a method for quantifying cells with internalized magnetic nanowires (NWs). A machine learning-based computational framework, CellCognition, is adapted and used to classify cells with internalized and no internalized NWs, labeled with the fluorogenic pH-dependent dye pHrodo™ Red, and subsequently to determine the percentage of cells with internalized NWs at different time points. In a "proof-of-concept", we performed a study on human colon carcinoma HCT 116 cells and human epithelial cervical cancer HeLa cells interacting with iron (Fe) and nickel (Ni) NWs. CONCLUSIONS: This study reports a novel method for the quantification of cells that internalize a specific type of nanostructures. This approach is suitable for high-throughput and real-time data analysis and has the potential to be used to study the interaction of different types of nanostructures in live-cell assays.

On-Chip Magnetic Bead Manipulation and Detection Using a Magnetoresistive Sensor-Based Micro-Chip: Design Considerations and Experimental Characterization.

The remarkable advantages micro-chip platforms offer over cumbersome, time-consuming equipment currently in use for bio-analysis are well documented. In this research, a micro-chip that includes a unique magnetic actuator (MA) for the manipulation of superparamagnetic beads (SPBs), and a magnetoresistive sensor for the detection of SPBs is presented. A design methodology, which takes into account the magnetic volume of SPBs, diffusion and heat transfer phenomena, is presented with the aid of numerical analysis to optimize the parameters of the MA. The MA was employed as a magnetic flux generator and experimental analysis with commercially available COMPEL™ and Dynabeads(®) demonstrated the ability of the MA to precisely transport a small number of SPBs over long distances and concentrate SPBs to a sensing site for detection. Moreover, the velocities of COMPEL™ and Dynabead(®) SPBs were correlated to their magnetic volumes and were in good agreement with numerical model predictions. We found that 2.8 µm Dynabeads(®) travel faster, and can be attracted to a magnetic source from a longer distance, than 6.2 µm COMPEL™ beads at magnetic flux magnitudes of less than 10 mT. The micro-chip system could easily be integrated with electronic circuitry and microfluidic functions, paving the way for an on-chip biomolecule quantification device.

A Magnetoresistive Tactile Sensor for Harsh Environment Applications.

A magnetoresistive tactile sensor is reported, which is capable of working in high temperatures up to 140 °C. Hair-like bioinspired structures, known as cilia, made out of permanent magnetic nanocomposite material on top of spin-valve giant magnetoresistive (GMR) sensors are used for tactile sensing at high temperatures. The magnetic nanocomposite, consisting of iron nanowires incorporated into the polymer polydimethylsiloxane (PDMS), is very flexible, biocompatible, has high remanence, and is also resilient to antagonistic sensing ambient. When the cilia come in contact with a surface, they deflect in compliance with the surface topology. This yields a change of the GMR sensor signal, enabling the detection of extremely fine features. The spin-valve is covered with a passivation layer, which enables adequate performance in spite of harsh environmental conditions, as demonstrated in this paper for high temperature.

Smart Sensing System for the Prognostic Monitoring of Bone Health.

The objective of this paper is to report a novel non-invasive, real-time, and label-free smart assay technique for the prognostic detection of bone loss by electrochemical impedance spectroscopy (EIS). The proposed system incorporated an antibody-antigen-based sensor functionalization to induce selectivity for the C-terminal telopeptide type one collagen (CTx-I) molecules-a bone loss biomarker. Streptavidin agarose was immobilized on the sensing area of a silicon substrate-based planar sensor, patterned with gold interdigital electrodes, to capture the antibody-antigen complex. Calibration experiments were conducted with various known CTx-I concentrations in a buffer solution to obtain a reference curve that was used to quantify the concentration of an analyte in the unknown serum samples. Multivariate chemometric analyses were done to determine the performance viability of the developed system. The analyses suggested that a frequency of 710 Hz is the most discriminating regarding the system sensitivity. A detection limit of 0.147 ng/mL was achieved for the proposed sensor and the corresponding reference curve was linear in the range of 0.147 ng/mL to 2.669 ng/mL. Two sheep blood samples were tested by the developed technique and the results were validated using enzyme-linked immunosorbent assay (ELISA). The results from the proposed technique match those from the ELISA.

Future Thread: Printing Electronics on Fibers.

This article introduces a methodology to increase the integration density of functional electronic features on fibers/threads/wires through additive deposition of functional materials via printed electronics. It opens the possibility to create a multifunctional intelligent system on a single fiber/thread/wire while combining the advantages of existing approaches, i.e., the scalability of coating techniques and the microfeatures of semiconductor-based fabrication. By directly printing on threads (of diameters ranging from 90 to 1000 µm), micropatterned electronic devices and multifunctional electronic systems could be formed. Contact and noncontact printing methods were utilized to create various shapes from serpentines and meanders to planar coils and interdigitated electrodes, as well as complex multilayer structures for thermal and light actuators, humidity, and temperature sensors. We demonstrate the practicality of the method by integrating a multifunctional thread into a FFP mask for breath monitoring. Printing technologies provide virtually unrestricted choices for the types of threads, materials, and devices used. They are scalable via roll-to-roll processes and offer a resource-efficient way to democratize electronics across textile products.

Wearable sensors for monitoring marine environments and their inhabitants.

Human societies depend on marine ecosystems, but their degradation continues. Toward mitigating this decline, new and more effective ways to precisely measure the status and condition of marine environments are needed alongside existing rebuilding strategies. Here, we provide an overview of how sensors and wearable technology developed for humans could be adapted to improve marine monitoring. We describe barriers that have slowed the transition of this technology from land to sea, update on the developments in sensors to advance ocean observation and advocate for more widespread use of wearables on marine organisms in the wild and in aquaculture. We propose that large-scale use of wearables could facilitate the concept of an 'internet of marine life' that might contribute to a more robust and effective observation system for the oceans and commercial aquaculture operations. These observations may aid in rationalizing strategies toward conservation and restoration of marine communities and habitats.

Current-induced zero-field domain wall depinning in cylindrical nanowires.

Multi-segmented cylindrical nanowires have properties that make them attractive for high-density, high-speed logic and memory applications. Investigations of the current-induced domain wall motion in cylindrical nanowires have, so far, typically been conducted with a background magnetic field. However, if performed at zero external field, they would be much more viable for their use in prospective electronic devices. Here, we present an all-magneto electrical method to consistently pin domain walls in multi-segmented nanowires and induce their de-pinning using current pulses. The experiments were conducted with compositionally modulated three-segmented nickel/cobalt/nickel and two-segmented cobalt/nickel nanowires of 190 and 150 nm diameter, respectively, where the soft/hard magnetic texture has been fairly studied. We find that for the 3 segmented nanowire, the domain wall can be de-pinned independent of the polarity of the pulse, while for the 2 segmented nanowire the domain wall de-pins only for one polarity. Applying current pulses of 1 × 1012 A/m2, we use a pulse width of 22 ns to estimate a lower boundary for the domain wall speed of 634.54 m/s in cobalt. We study the resistive heating effect from the DC measurement current to find a temperature increase of no more than 2 °C after more than 20 h of tests.

Smartphone-Based Multiplexed Biosensing Tools for Health Monitoring.

Many emerging technologies have the potential to improve health care by providing more personalized approaches or early diagnostic methods. In this review, we cover smartphone-based multiplexed sensors as affordable and portable sensing platforms for point-of-care devices. Multiplexing has been gaining attention recently for clinical diagnosis considering certain diseases require analysis of complex biological networks instead of single-marker analysis. Smartphones offer tremendous possibilities for on-site detection analysis due to their portability, high accessibility, fast sample processing, and robust imaging capabilities. Straightforward digital analysis and convenient user interfaces support networked health care systems and individualized health monitoring. Detailed biomarker profiling provides fast and accurate analysis for disease diagnosis for limited sample volume collection. Here, multiplexed smartphone-based assays with optical and electrochemical components are covered. Possible wireless or wired communication actuators and portable and wearable sensing integration for various sensing applications are discussed. The crucial features and the weaknesses of these devices are critically evaluated.

Minimally-invasive, real-time, non-destructive, species-independent phytohormone biosensor for precision farming.

To keep up with population growth, precision farming technologies must be implemented to sustainably increase agricultural output. The impact of such technologies can be expanded by monitoring phytohormones, such as salicylic acid. In this study, we present a plant-wearable electrochemical sensor for in situ detection of salicylic acid. The sensor utilizes microneedle-based electrodes that are functionalized with a layer of salicylic acid selective magnetic molecularly imprinted polymers. The sensor's capability to detect the phytohormone is demonstrated both in vitro and in vivo with a limit of detection of 2.74 µM and a range of detection that can reach as high as 150 µM. Furthermore, the selectivity of the sensor is verified by testing the sensor on commonly occurring phytohormones. Finally, we demonstrate the capability of the sensor to detect the onset of fungal infestation in Tobacco 5 min post-inoculation. This work shows that the sensor could serve as a promising platform for continuous and non-destructive monitoring in the field and as a fundamental research tool when coupled with a portable potentiostat.

Distinguishing Local Demagnetization Contribution to the Magnetization Process in Multisegmented Nanowires.

Cylindrical magnetic nanowires are promising materials that have the potential to be used in a wide range of applications. The versatility of these nanostructures is based on the tunability of their magnetic properties, which is achieved by appropriately selecting their composition and morphology. In addition, stochastic behavior has attracted attention in the development of neuromorphic devices relying on probabilistic magnetization switching. Here, we present a study of the magnetization reversal process in multisegmented CoNi/Cu nanowires. Nonstandard 2D magnetic maps, recorded under an in-plane magnetic field, produce datasets that correlate with magnetoresistance measurements and micromagnetic simulations. From this process, the contribution of the individual segments to the demagnetization process can be distinguished. The results show that the magnetization reversal in these nanowires does not occur through a single Barkhausen jump, but rather by multistep switching, as individual CoNi segments in the NW undergo a magnetization reversal. The existence of vortex states is confirmed by their footprint in the magnetoresistance and 2D MFM maps. In addition, the stochasticity of the magnetization reversal is analysed. On the one hand, we observe different switching fields among the segments due to a slight variation in geometrical parameters or magnetic anisotropy. On the other hand, the stochasticity is observed in a series of repetitions of the magnetization reversal processes for the same NW under the same conditions.

Integrated Magnetohydrodynamic Pump with Magnetic Composite Substrate and Laser-Induced Graphene Electrodes.

An integrated polymer-based magnetohydrodynamic (MHD) pump that can actuate saline fluids in closed-channel devices is presented. MHD pumps are attractive for lab-on-chip applications, due to their ability to provide high propulsive force without any moving parts. Unlike other MHD devices, a high level of integration is demonstrated by incorporating both laser-induced graphene (LIG) electrodes as well as a NdFeB magnetic-flux source in the NdFeB-polydimethylsiloxane permanent magnetic composite substrate. The effects of transferring the LIG film from polyimide to the magnetic composite substrate were studied. Operation of the integrated magneto hydrodynamic pump without disruptive bubbles was achieved. In the studied case, the pump produces a flow rate of 28.1 µL/min. while consuming ~1 mW power.

Robust, Long-Term, and Exceptionally Sensitive Microneedle-Based Bioimpedance Sensor for Precision Farming.

Precision farming has the potential to increase global food production capacity whilst minimizing traditional inputs. However, the adoption and impact of precision farming are contingent on the availability of sensors that can discern the state of crops, while not interfering with their growth. Electrical impedance spectroscopy offers an avenue for nondestructive monitoring of crops. To that end, it is reported on the deployment of impedimetric sensors utilizing microneedles (MNs) that can be used to pierce the waxy exterior of plants to obtain sensitive impedance spectra in open-air settings with an average relative noise value of 3.83%. The sensors are fabricated using a novel micromolding and release method that is compatible with UV photocurable and thermosetting polymers. Assessments of the quality of the MNs under scanning electron microscopy show that the replication process is high in fidelity to the original design of the master mold and that it can be used for upward of 20 replication cycles. The sensor's performance is validated against conventional planar sensors for obtaining the impedance values of Arabidopsis thaliana. As a change is detected in impedance due to lighting and hydration, this raises the possibility for their widespread use in precision farming.

Anatomical study of the radius and center of curvature of the distal femoral condyle.

In this anatomical study, the anteroposterior curvature of the surface of 16 cadaveric distal femurs was examined in terms of radii and center point. Those two parameters attract high interest due to their significance for total knee arthroplasty. Basically, two different conclusions have been drawn in foregoing studies: (1) The curvature shows a constant radius and (2) the curvature shows a variable radius. The investigations were based on a new method combining three-dimensional laser-scanning and planar geometrical analyses. This method is aimed at providing high accuracy and high local resolution. The high-precision laser scanning enables the exact reproduction of the distal femurs-including their cartilage tissue-as a three-dimensional computer model. The surface curvature was investigated on intersection planes that were oriented perpendicularly to the surgical epicondylar line. Three planes were placed at the central part of each condyle. The intersection of either plane with the femur model was approximated with the help of a b-spline, yielding three b-splines on each condyle. The radii and center points of the circles, approximating the local curvature of the b-splines, were then evaluated. The results from all three b-splines were averaged in order to increase the reliability of the method. The results show the variation in the surface curvatures of the investigated samples of condyles. These variations are expressed in the pattern of the center points and the radii of the curvatures. The standard deviations of the radii for a 90 deg arc on the posterior condyle range from 0.6 mm up to 5.1 mm, with an average of 2.4 mm laterally and 2.2 mm medially. No correlation was found between the curvature of the lateral and medial condyles. Within the range of the investigated 16 samples, the conclusion can be drawn that the condyle surface curvature is not constant and different for all specimens when viewed along the surgical epicondylar axis. For the portion of the condylar surface that articulates with the tibia during knee flexion-extension, the determined center points approximate the location of the centers of rotation. The results suggest that the concept of a fixed flexion-extension axis is not applicable for every specimen.

Biofunctionalization of Magnetic Nanomaterials.

Magnetic nanomaterials have received great attention in different biomedical applications. Biofunctionalizing these nanomaterials with specific targeting agents is a crucial aspect to enhance their efficacy in diagnostics and treatments while minimizing the side effects. The benefit of magnetic nanomaterials compared to non-magnetic ones is their ability to respond to magnetic fields in a contact-free manner and over large distances. This allows to guide or accumulate them, while they can also be monitored. Recently, magnetic nanowires (NWs) with unique features were developed for biomedical applications. The large magnetic moment of these NWs enables a more efficient remote control of their movement by a magnetic field. This has been utilized with great success in cancer treatment, drug delivery, cell tracing, stem cell differentiation or magnetic resonance imaging. In addition, the NW fabrication by template-assisted electrochemical deposition provides a versatile method with tight control over the NW properties. Especially iron NWs and iron-iron oxide (core-shell) NWs are suitable for biomedical applications, due to their high magnetization and low toxicity. In this work, we provide a method to biofunctionalize iron/iron oxide NWs with specific antibodies directed against a specific cell surface marker that is overexpressed in a large number of cancer cells. Since the method utilizes the properties of the iron oxide surface, it is also applicable to superparamagnetic iron oxide nanoparticles. The NWs are first coated with 3-aminopropyl-tri-ethoxy-silane (APTES) acting as a linker, which the antibodies are covalently attached to. The APTES coating and the antibody biofunctionalization are proven by electron energy loss spectroscopy (EELS) and zeta potential measurements. In addition, the antigenicity of the antibodies on the NWs is tested by using immunoprecipitation and western blot. The specific targeting of the biofunctionalized NWs and their biocompatibility are studied by confocal microscopy and a cell viability assay.

3D Printed Microneedle Array for Electroporation.

In-vitro transfection of cells by electroporation is a widely used approach in cell biology and medicine. The transfection method is highly dependent on the cell culture's electrical resistance, which is strongly determined by differences in the membranes, but also on the morphology of the electrodes. Microneedle (MN)-based electrodes have been used to concentrate the electrical field during electroporation, and therefore maximize its effect on cell membrane permeability. So far, the methods used for the fabrication of MN electrodes have been relatively limited with respect to the needle design. In this work, we provide a method to fabricate MNs using 3D printing, which is a technology that provides a high degree of flexibility with respect to geometry and dimensions. Pyramidal-shaped MN designs were fabricated and tested on HCT116 cancer cells. Customization of the tips of the pyramids permits tailoring of the electrical field in the vicinity of the cell membranes. The fabricated device enables low-voltage (2 V) electroporation, eliminating the need for the use of specialized chemical buffers. The results show the potential of this method, which can be exploited and optimized for many different applications, and offer a very accessible approach for in-vitro electroporation and cell studies. The MNs can be customized to create complex structures, for example, for a multi-culture cell environment.