Magnetic nanowires (MNWs) were explored as potential magnetic tags for cell detection with giant magnetoresistance (GMR) biosensors based on a handheld system. Due to size, shape anisotropy and higher moment materials, the signal detected from a single MNW was 2500 times larger than that from a single magnetic iron oxide nanobead, which is important for ultra-low concentration cell detection. A model was used to determine how the MNW orientation with respect to the GMR sensor impacts detection performance, and the results aligned well with the experimental results. As a proof of concept OSCA-8 cells tagged with Ni MNWs were also detected using the same handheld system. The limit of detection (LOD) in aqueous solution appeared to be 133 cells, and single-cell detection can be realized if the cell is in direct contact with the sensor surface. Since MNWs are already employed in magnetic separation of cells, directly using MNWs as tags in cell detection eliminates the need of additional functionalization with other labels. This largely simplifies the detection process and reduces the risk of contamination during sample preparation.

Increasing interest has been given in recent years to alternative physical therapies for cancer, with a special focus on magneto-mechanical actuation of magnetic nanoparticles. The reported findings underline the need for highly biocompatible nanostructures, along with suitable mechanical and magnetic properties for different configurations of alternating magnetic fields. Here, we show how the biocompatibility of magnetic nanowires (MNWs), especially CoFe, can be increased by gold coating, which can be used both in cancer therapy and magnetic resonance imaging (MRI). This study provides a new approach in the field of theranostic applications, demonstrating the capabilities of core–shell nanowires to be used both to increase the cancer detection limit (as T2 contrast agents) and for its treatment (through magneto-mechanical actuation). The MNWs were electrodeposited in alumina templates, whereas the gold layer was electroless-plated by galvanic replacement. The gold-coated CoFe nanowires were biocompatible until they induced high cellular death to human osteosarcoma cells via magneto-mechanical actuation. These same MNWs displayed increased relaxivities (r1, r2). Our results show that the gold-coated CoFe nanowires turned out to be highly efficient in tumor cell destruction, and, at the same time, suitable for MRI applications.

Magnetic nanowires (MNWs) can have their moments reversed via several mechanisms that are controlled using the composition, length, diameter, and density of nanowires in arrays as-synthesized or as individual nanoparticles in assays or gels. This tailoring of magnetic reversal leads to unique properties that can be used as a signature for reading out the type of MNW for applications as nano-barcodes. When synthesized inside track-etched polycarbonate membranes, the resulting MNW-embedded membranes can be used as biocompatible bandaids for detection without contact or optical sighting. When etched out of the growth template, free-floating MNWs are internalized by cells at 37 °C such that cells and/or exosomes can be collected and detected. In applications of cryopreservation, MNWs can be suspended in cryopreservation agents (CPAs) for injection into the blood vessels of tissues and organs as they are vitrified to -200 °C. Using an alternating magnetic field, the MNWs can then be nanowarmed rapidly to prevent crystallization and uniformly to prevent cracking of specimens, for example, as grafts or transplants. This invited paper is a review of recent progress in the specific bioapplications of MNWs to barcodes, biocomposites, and nanowarmers.

Magnetic nanoparticles (MNPs) are playing an increasing role in medical applications, becoming an important tool for cancer detection. In this study, magnetic core-shell CoFe@Au nanowires with optimized biocompatibility, as well as multilayered Au/CoFe/Au nanowires are synthetized by using electrodeposition and electroless-plating techniques. Their morphology and composition are investigated, the materials being tested for their use as T2 contrast agents in MRI. A dramatic increase of r1 and r2 relaxivity values was obtained for the CoFe@Au core-shell nanowires, making these materials best candidates as new MRI contrast agents.

Isolating tumor exosomes (TEX) secreted by cancer cells can provide valuable information about the state of a tumor. Here, we present a method to rapidly isolate TEX using magnetic nanowires (MNWs). Specifically, two sets of Fe/Au segmented MNWs were used to isolate TEX released by canine osteosarcoma cell lines (OSCA 8, 32, and 40). These MNWs were prepared by electrodeposition showcasing similar length (2.2(1) mu m) and diameter (36(3) nm) but different Fe/Au segment thickness: 120(20)/30(6) nm (sample A) and 28(7)/3(1) nm (sample B). Magnetic measurements indicate that we can effectively tune the magnetic response of the MNWs by changing their segment thickness, obtaining a more anisotropic behavior for sample A. The internalization of these MNWs by OSCA cells as a function of their concentration has been followed by fluorescence microscopy, and a concentration around 25 mu g of Fe/Au MNWs per 3 x 10(5) cells has been defined as optimal. Electron microscopy images have revealed that, once internalized, these MNWs end up residing within lysosomes inside the cancer cells, where they tend to be degraded (especially the Fe segments) and fragmented into smaller pieces. Lower degradation for sample B has been observed and related to differences in the synthesis/functionalization process of both samples. We have hypothesized that these fragments of Fe/ Au MNWs are packaged into TEX released to the medium which can then be isolated via a magnetic stand. This has been tested by carrying out TEX isolation experiments on the OSCA cell and comparing the magnetically isolated TEX with those isolated by using conventional methods based on centrifugation. Nanoparticle tracking analysis (NanoSight) has confirmed that the TEX isolated with MNWs have a comparable size distribution and yield to those obtained by using conventional methods, indicating that our magnetic isolation method can consistently provide relatively high TEX yields in a low-cost and fast way.

Ferromagnetic Co35Fe65, Fe, Co, and Ni nanowires have high saturation magnetizations (Ms) and magnetic anisotropies, making them ideal for magnetic heating in an alternating magnetic field (AMF). Here, Au-tipped nanowires were coated with polyethylene glycol (PEG) and specific absorption rates (SAR) were measured in glycerol. SAR increased when using metals with increasing Ms (Co35Fe65 > Fe > Co > Ni), reaching 1610 ± 20 W g-1 metal at 1 mg metal per ml glycerol for Co35Fe65 nanowires using 190 kHz and 20 kA m-1. Aligning these nanowires parallel to the AMF increased SAR up to 2010 W g-1 Co35Fe65. Next, Co35Fe65 nanowires were used to nanowarm vitrified VS55, a common cryoprotective agent (CPA).Nanowarming rates up to 1000 °C min-1 (5 mg Co35Fe65 per ml VS55) were achieved, which is 20× faster than the critical warming rate (50 °C min-1) for VS55 and other common CPAs. Human dermal fibroblast cells exposed to VS55, and Co35Fe65 nanowire concentrations of 0, 1 and 2.5 mg Fe per ml all showed similar cell viability, indicating that the nanowires had minimal cytotoxicity. With the ability to provide rapid and uniform heating, ferromagnetic nanowires have excellent potential for nanowarming cryopreserved tissues.

We are developing segmented magnetic nanowires (MNWs) as a new platform for highly specific biolabels. We found that cancer cells internalize MNWs and package them into exosomes, which are then secreted for several days. These MNWs thus enable magnetic isolation of exosomes, which could prove useful in future diagnosis. Our immediate goals are to study how cells internalize MNWs, to determine the timing and reproducibility of exosome secretion, and to improve the magnetic isolation of exosomes. Following this work, we aim to use ferromagnetic resonance (FMR) to identify specific MNW biolabels, similar to radio frequency identification (RFID).In this study, we incubated osteosarcoma (OSCA-8) cells with Fe/Au segmented MNWs with and without PEG coating for 48 hours. Internalization of MNWs as a function of concentration (5-40 µg/ml) was followed by fluorescence and transmission electron microscopy (TEM). We obtained quantitative estimates of MNW internalization by magnetic measurements. Our experiments indicated better internalization of the MNWs using PEG as a capping agent. As we increased the concentration of MNWs, both the number of cells with MNWs and the number of MNWs per cell increased. TEM images show that after uptake by cancer cells, MNWs were predominantly located within lysosomes, and they appeared to be fragmented into small segments of similar size as exosomes. These segments were mostly composed of either Fe or Au, suggesting that fragmentation occurred at or near the boundary of segments.We used two different methods for exosome isolation: non-magnetic isolation (centrifuge and ExoQuick TC) as a control and magnetic isolation. We incubated OSCA-8 cells with different concentrations of MNWs (0 to 35 µg/ml), and exosomes were isolated for up to 11 days. We analyzed the exosome size distribution using a nanoparticle tracking analyzer (NanoSight) and found that exosomes isolated magnetically had similar size distributions as those isolated non-magnetically. A minimum concentration of 25 µg/ml MNWs in 3×105 cells was required for appreciable magnetic isolation. Increasing the concentration of MNWs progressively; however, isolated microvesicles that had wider and more heterogeneous size distributions.Next, we successfully identified two different types of MNW biolabels by FMR. MNWs were fixed in a polymer that was placed onto an RFID chip. Each type of MNW exhibited a unique RF signature as the sample was exposed to an external magnetic field.Our preliminary data show that MNWs appear to allow fast, inexpensive magnetic exosome isolation and is our future goal is MNW identification of exosomes. The methodology developed in this study should be transferable to develop comparable approaches to isolate and identify exosomes from virtually any type of cell.Citation Format: Zohreh Nemati, Thomas Gage, Mohammad Reza Zamani Kouhpanji, Joseph Um, Alicia Donnelly, Daniel Shore, Kelly Makielski, Yali Zhang, Rhonda Franklin, Jaime F. Modiano, Bethanie J. Stadler. Magnetic isolation and identification of exosomes using Fe/Au nanowires [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1341.

Collagen matrices are one form of artificial tissue that has applications in biomimetic organs or tumors, and in fundamental biology. Anatomical organs and tissues are often composed of aligned collagen, and in this study cross-linking nickel magnetic nanowires (MNWs) to collagen allowed a one-step bidirectional alignment of the collagen matrices when processed in a uniform magnetic field. These matrices were analyzed by differential interference contrast (DIC) microscopy, scanning electron microscopy (SEM) and polarized transmittance. The bi-directional alignment was also confirmed by plated, stained arachnoid cells from the blood-brain-barrier (BBB). Arachnoid cells are morphologically sensitive to their extracellular matrix (ECM) environment, and in this study, they were observed to spider out in two distinct directions as predicted by microscopy and transmittance. In fact, MNW-collagen matrices plated with arachnoid-cells are promising for future studies of artificial BBBs. Other cells (here osteosarcoma) have been observed to internalize MNWs, which leads to the possibility of barcoding matrices and cells with distinct signatures, pending a magnetic readout technique. To this aim, mixtures of two different MNW populations were analyzed using first order reversal curves (FORC), and the relative concentrations of the two populations were correctly estimated with negligible error for ratios of 1: 23 and only 7% error for ratios of 1: 115. Together, these studies open a path for magnetic identification of artificial tissues where distinct magnetic labels on matrices and in cells combine for a unique fingerprint. (C) 2017 Published by Elsevier B.V.

Galfenol (Fe1-xGax, 10 < x < 40) may be the only smart material that can be made by electrochemical deposition which enables thick film and nanowire structures. This article reviews the deposition, characterization, and applications of Galfenol thin films and nanowires. Galfenol films have been made by sputter deposition as well as by electrochemical deposition, which can be difficult due to the insolubility of gallium. However, a stable process has been developed, using citrate complexing, a rotating disk electrode, Cu seed layers, and pulsed deposition. Galfenol thin films and nanowires have been characterized for crystal structures and magnetostriction both by our group and by collaborators. Films and nanowires have been shown to be largely polycrystalline, with magnetostrictions that are on the same order of magnitude as textured bulk Galfenol. Electrodeposited Galfenol films were made with epitaxial texture on GaAs. Galfenol nanowires have been made by electrodeposition into anodic aluminum oxide templates using similar parameters defined for films. Segmented nanowires of Galfenol/Cu have been made to provide engineered magnetic properties. Applications of Galfenol and other magnetic nanowires include microfluidic sensors, magnetic separation, cellular radio-frequency identification (RFID) tags, magnetic resonance imaging (MRI) contrast, and hyperthermia.

Epitope-specific CD4+ T lymphocytes were magnetically enriched using ferromagnetic Ni and Fe-Au nanowires coated with a monomer containing a major histocompatibility complex class II-bound peptide epitope (pMHCII). The enriched lymphocytes were subsequently quantified using fluorescence-activated cell sorting (FACS). This was the first use of magnetic nanowires for cell sorting using FACS, and improvements in both specificity and fluorescent signal strength were predicted due to higher particle moments and lengths than conventional paramagnetic beads. Three different types of nanowires (Ni, Fe with Au tip and Fe-Au multilayers) were made by electrodeposition. Ni nanowires separated fewer T cells than Au tipped Fe nanowires, likely because Ni has a lower magnetic moment than Fe. Fe-Au multilayer nanowires separated more T cells than Au-tipped Fe nanowires because there was more monomer per nanowire. Also, increasing the amount of monomer increased the number of CD4+ cells separated. Compared to conventional paramagnetic beads, the nanowires had lower specificity for CD4+ T cells, but had stronger fluorescent signals due to more fluorophores per particle. This results in broader FACS baseline separation between the positive and negative cells, which is useful to detect T cells, even those with lower binding affinity for pMHCII ligands.

Among all transition metals magnetic alloys, Co35Fe65 possesses the highest saturation magnetization B-S = 2.45 T at room temperature given by the so-called "Slater-Pauling limit". For controlled electrodeposition of Co35Fe65 nanowire arrays the following parameters were found to be optimal: electrolyte solution with 1-2 mM malonic acid (MA), ionic ratio Fe+2/Co+2 = 2.0, growth rate, and pulsed potential deposition with time-on (2.5 s) at the potential of -1.15 V/SCE and time-off (1.0 s) at -0.70 V/SCE. These arrays were deposited inside anodic aluminum oxide (AAO) templates that contained columnar nanopores with diameters either 35 or 200 nm. Cyclic voltammetry was used in solution with and without MA and reaction mechanism was proposed to explain the critical role of MA in electrodeposition of CoFe alloys. In addition to uniform deposition of stechiometric Co35Fe65 alloys, a selectivity ratio, (SR) similar to 1.0, were achieved, which means that the atomic ratio of Fe/Co in the nanowire matched the molar ratio of Fe+2/Co+2 in the electrolyte. The magnetic behavior of the subsequent 2.45 T Co35Fe65 nanowire arrays showed that the shape and magnetostatic anisotropies dominated the effective anisotropy, and the impact of magnetocrystalline and magnetelastic anisotropies field was very small. (C) The Author(s) 2016. Published by ECS. All rights reserved.

Electrodeposited Fe and Fe-Au nanowires were studied for potential as MRI contrast agents, especially for T2-weighted imaging. Transverse relaxivities up to r2 = 77.1 mM Fe-1 s-1 (at 1.5 T) were achieved when Fe-Au nanowires were coated with thiol and carboxylic acid functionalized poly(ethyleneglycol). T2-Weighted images (9 T) verified successful contrast.

We present non-cytotoxic, magnetic, Arg-Gly-Asp (RGD)-functionalized nickel nanowires (RGD–nanowires) that trigger specific cellular responses via integrin transmembrane receptors, resulting in dispersal of the nanowires. Time-lapse fluorescence and phase contrast microscopy showed that dispersal of 3 μm long nanowire increased by a factor of 1.54 with functionalization by RGD, compared to polyethylene glycol (PEG), through integrin-specific binding, internalization and proliferation in osteosarcoma cells. Further, a 35.5% increase in cell density was observed in the presence of RGD–nanowires, compared to an increase of only 15.6% with PEG–nanowires. These results promise to advance applications of magnetic nanoparticles in drug delivery, hyperthermia, and cell separation where uniformity and high efficiency in cell targeting is desirable.